Skip to main content
NCBI home page
Journal of Anatomy logoLink to Journal of Anatomy
. 2015 Oct 15;227(5):673–685. doi: 10.1111/joa.12380

Development of the ventral body wall in the human embryo

Hayelom K Mekonen 1, Jill P J M Hikspoors 1, Greet Mommen 1, S Eleonore Köhler 1, Wouter H Lamers 1,2
PMCID: PMC4609202  PMID: 26467243

Abstract

Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ∼ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira® reconstruction and cinema 4D® remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage (CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the ‘closure’ of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body.

Keywords: abdominal muscles, dorsoventral differential growth, infraumbilical body wall, ventral body wall

Introduction

The ventral body wall that we consider in this study surrounds the body cavities and develops from both somitic and lateral plate mesoderm. In vertebrates, all muscles develop from the somitic dermomyotomes (Wachtler & Christ, 1992; Dietrich et al. 1998). The muscle cells of the ventral body wall develop from the lateral or hypaxial half of the dermomyotome and are innervated by the ventral branch of the spinal nerves (Ordahl & Le Douarin, 1992). In mammals, the axial skeleton and osseous parts of the ribs develop from somitic mesoderm, whereas the sternum and appendicular skeleton develop from the lateral plate mesoderm (Durland et al. 2008; Shearman & Burke, 2009; Buchholtz, 2014). Muscles which develop entirely within a somitic environment are defined as ‘primaxial’, whereas those that are surrounded by lateral-plate mesoderm are defined as ‘abaxial’ (Nowicki & Burke, 2000). Accordingly, the abaxial and primaxial muscle classification originates from the embryonic source of the development, whereas the hypaxial and epaxial muscle grouping arises from their different innervations by ventral and dorsal rami, respectively (Nowicki & Burke, 2000). The transition from a fully primaxial somitic cell population to a mixed population of somitic myoblasts and surrounding tissue from the lateral plate is known as the ‘somitic frontier’ (Nowicki et al. 2003; Shearman & Burke, 2009) and appears to correspond to the expression of the paired-related homeobox1 gene (Prx1) (Durland et al. 2008; Shearman & Burke, 2009).

The complex developmental history of the ventral body wall is reflected in its malformations. Defects in the primaxial component are often linked to neural tube-closure defects, whereas defects in the abaxial component manifest themselves as limb-body wall or ventral body wall defects (Iimura et al. 2009; Shearman & Burke, 2009; Hunter et al. 2011). Several hypotheses with respect to ventral body wall defects exist (Brewer & Williams, 2004; Hunter et al. 2011) and none is unopposed. We have interpreted the description of the development of the body wall in the previous paragraph as revealing that the dorsomedial parts of the ventral body wall develop entirely from the paraxial mesoderm which eventually forms both non-migratory (interlimb) and migratory (appendicular, tongue, and diaphragm) hypaxial muscles (Buckingham et al. 2003; Vasyutina & Birchmeier, 2006), whereas the bones and connective tissue of the ventromedial parts develop from the lateral plate mesoderm and are initially found laterally rather than ventrally relative to the dorsomedial part of the ventral body wall (Chevallier, 1979; Christ et al. 1983). The changing position of the lateral somitic frontier (Durland et al. 2008) and associated muscles (Evans et al. 2006), the near absence of body-wall muscles in Prune belly syndrome (Hassett et al. 2012), and the midline position of ventral body wall defects have been interpreted as a ventralward migration of somitic cells. However, the embryo also increases ∼ 25-fold in volume while these definitive anatomic relations are established. It is, therefore, well possible that the described changes in topography are apparent only and are accounted for by differential growth. Unfortunately, few, if any, three-dimensional visualizations and size measurements of the components of the developing ventral body wall are available. We, therefore, set out to reinvestigate the development of the ventral body wall with the aim to describe the changing topography of the constituting structures and to provide a high-quality visual account of the successive steps in its development.

Materials and methods

Embryos

This study was undertaken in accordance with the Dutch regulation for the proper use of human tissue for medical research purposes. We included anonymous specimens from the historical collections of embryos and fetuses of the Departments of Anatomy & Embryology, Leiden University Medical Center (LUMC), Leiden, and the Academic Medical Center (AMC), Amsterdam, The Netherlands, and the Carnegie Collection, Washington, DC, USA [obtained via the Digitally Reproduced Embryonic Morphology (DREM) project] that were donated for scientific research. The current investigation studied human embryos between 4 (CS13) and 10 weeks of development. The developmental stages of all embryos in the embryonic period proper (4–8 weeks of development) were expressed in Carnegie stages according to the criteria of O'Rahilly & Muller (2010). The return of the physiological hernia at 9 weeks of development (Blaas & Eik-Nes, 2009) was used to estimate the age of the embryos after Carnegie stage 23 (Wisser et al. 1994; Loughna et al. 2009).

Antibodies

The embryos and antibodies described in Fig.1 were originally reported by Wessels et al. (1990, 1991). These sections demonstrate the position of the muscle primordia before they can be identified as such by histological criteria and the ramification of the spinal nerve. The antibody directed against myosin heavy chain β (MYH7) identifies the primary myoblasts and that against a common epitope of creatine kinase (CK) M and B.

Fig 1.

Fig 1

Open in a new tab

Myotome development in early human embryos. Myosin heavy chain β was observed in a ‘primary myotome’ at a lower cervical segment at CS14 (panel A). Panels (B–D) show an immunhistochemical staining against creatine kinase M + B, which delineates the ventral boundary of the myotomes that have extended ventrolaterally in the developing lateral body wall. The dorsalmost boundary of the myotome, on the other hand, did not extend dorsally beyond the limiting furrow in the spinal cord. Panels (C) and (D) show separate epaxial and hypaxial myotomal compartments with separate dorsal and ventral spinal nerves. Note that the entire myotome (#) in each panel develops lateral of the ventral spinal nerve (*). Arrowheads: notochord in the center of the developing vertebral body; *ventral spinal nerve; +dorsal spinal nerve; #muscle anlagen; double arrowhead: lateral cutaneous nerve; A: vertebral arch; Ep and Hyp: epaxial and hypaxial parts of the myotome, respectively; SG: spinal ganglion. Scale bars: 0.05 mm.

3D reconstructions and measurements

Histological sections of human embryos were scanned and digitized with an Olympus BX51 microscope and the DOTSLIDE program (Olympus, Zoeterwoude, The Netherlands). This program allows fully automated, high-resolution scanning of all sections on a glass slide. After conversion to JPEG images, the sections were aligned, segmented and analyzed using commercial software amira (version 6.0; base package; FEl Visualization Sciences Group Europe, Merignac Cedex, France). Initial alignment was performed automatically using the amira built-in least-square method. In addition, manual alignment was carried out to acquire an anatomically correct curvature of the body axis. MRI and high-resolution transvaginal three-dimensional sonography images (Pooh et al. 2011) of age-matched human embryos were used to realize the physiological curvature of the spine in the reconstructions. Bones and muscles were delineated manually in amira using a Wacom Intuos 5L tablet (487 × 318 × 12 mm). We analyzed the most developed stages and the least ambiguous structures in less developed stages first and proceeded from there to segmentation of structures with more gradual boundaries. Quality checks on the accuracy of the segmentation were possible because many of the reconstructed structures are repetitive (segmental) and bilaterally present. The distance between muscles, the size of the umbilical ring and the circumference of the dorsolateral body wall were all measured in the amira output. Data were analyzed by linear regression using spss version 21. A P-value < 0.05 was considered to be significant.

Visualization

Data obtained from the amira 3d software still showed the section contours and required smoothing to improve visualization of the respective structures. This was achieved by importing the data into cinema 4d (MAXON Computer GmbH, Friedrichsdorf, Germany). The ‘mesh’ function of cinema was used to create polygons that fitted the original amira muscle models. Once a muscle model was created, further smoothing was achieved with the ‘sculpting’ function. The remodeled muscles were checked for correspondence with their original amira output. Furthermore, cinema 4d enabled export of modeled structures via ‘wrl export’ into ADOBE portable device format (pdf) reader version 9 (http://www.adobe.com), which allows the generation of three-dimensional interactive PDF files (Supporting Information Figs S1–S6).

Results

Somitic phase of body wall development

In the human embryo, 38–39 somites develop bilaterally in the paraxial mesoderm between CS9 (∼ 26 days) and CS13 (∼ 32 days) (O'Rahilly & Muller, 2003). Sclerotome development begins when ∼ 10 somites have developed (CS10; ∼ 3 weeks; Corner, 1929; O'Rahilly & Müller, 1987; Monsoro-Burq, 2005), whereas (dermo-) myotome differentiation in chick and mouse embryos is first seen after > 20 somites have formed (Furst et al. 1989; Sacks et al. 2003). In agreement, we observed myosin heavy chain β expression in the ‘primary myotomes’ (Bothe et al. 2007) of human embryos at CS14 (Fig.1A). Between CS14 and CS18 (4.5–6.5 weeks of development), the creatine kinase-positive myotomes expanded on the lateral side of the spinal nerves (Fig.1B–D). If the neural tube is taken as reference structure, the (future) hypaxial portion of the myotome rapidly expanded ventrally between CS14 and CS18, whereas the (future) epaxial portion retained its lateral position during these stages and only began to expand dorsally thereafter. In mice, the myotome is not innervated until ED13.5 (approximately CS17) (Deries et al. 2008). In agreement, nerves were seen to penetrate into the developing epaxial and hypaxial portions of the myotome in Fig.1C (CS17) and 1D (CS18), whereas such a configuration was not yet present in CS15 embryos (Fig.1B). Furthermore, the lateral cutaneous nerve had become identifiable at this stage (double arrowhead in panels C and D), that is, also at a time point equivalent to the development in the mouse embryo (Munger & Munger, 1991). Because our present study concerns the ventral body wall, we focused on the development of the vertebrae, ribs and the interlimb hypaxial muscles. To follow the topographic changes of ventral body wall structures in the course of development, we have provided 3D pdfs of reconstructed embryos in Fig. S1, which allow an interactive inspection of our three-dimensional models.

Vertebral development

In the CS15 embryo (Fig.2), the ventromedial half of the somites had undergone an epithelial-to-mesenchymal transition and differentiated into loose and dense zones of the developing vertebrae. The zones with low and high cell density develop into the vertebral bodies and intervertebral disks, respectively (Verbout, 1985). In ventrolateral continuity with the disks, the rib anlagen developed (Verbout, 1985). In this CS15 embryo, the cells that form the vertebral bodies and intervertebral disks could be distinguished from those that form rib primordium (Fig.2D). In all stages studied, the vertebral column was bent ventrally into a concave curve, the so-called ‘primary curvature’ of the embryo (Taylor, 1975). The concave bend of the vertebral column at CS15 was accentuated in the lumbar region. This lumbar part of the vertebral column straightened concomitantly with the increase in the distance between the umbilical ring and the genital tubercle, that is, with the appearance of an infraumbilical region (see Formation of the intercostal and abdominal muscles). While the entire vertebral column straightened between 6 (CS17) and 9 weeks (Figs7), the concavity of the most distal (sacral) part was retained.

Fig 2.

Fig 2

Open in a new tab

Bones and muscles of the body wall in a CS15 (∼ 36 days) embryo. Panels (A) (ventral view) and (B) (lateral view) show the reconstructed vertebral column, ribs, umbilical ring (UR), and genital tubercle (GT), while panel (C) shows a section stained with Hematoxylin and Azophloxine (H&A) at the level indicated by a black line in panel (B). Note the short, laterally pointing ribs. Panels (A) and (B) show, in addition, the hypaxial (red) and epaxial (blue) myotomal compartments. Note that only the part of the hypaxial (red) myotomal compartment between the upper (UL) and lower limb (LL; both indicated by yellow circles) boundaries is shown here; and that the epaxial and hypaxial compartments are still connected between the developing ribs. Further note the shared wall of the caudal part of the umbilical ring (orange circle) and the genital tubercle (pale lilac). Panel (C) shows a histological section of the embryo used for this reconstruction, with the ribs (black arrow), hypaxial (red arrows) and epaxial (blue arrow) muscles. *Intervertebral disk; #vertebral body. A: vertebral arch; arrowhead: intercostal nerve. Scale bars: 0.2 mm. For 3D-PDF, see Fig. S1.

Fig 7.

Fig 7

Open in a new tab

Bones and hypaxial muscles of the ventral body wall of a 9-week embryo. Panels (A–C) show reconstructions of the vertebral column, ribs, umbilical ring (UR), genital tubercle (GT), rectus sheath (RS) and muscles of the body wall. In panels (D) and (E) lateral views of the reconstruction including the abdominal muscles and the rectus sheath are shown. Note the similarity in topography of the muscles with the CS23 embryo (cf. Fig.9 B–D and Table1). Panel (F) shows a transverse histological section of the 9-week embryo used for this reconstruction with the color-coded arrows identifying the respective muscles (cf. Fig.4 for the color code). Note that in panel (F), taken at the level indicated by a black line in (E), the transverse and internal oblique muscles are attached as a single layer to the rectus, whereas the large gap between the external oblique and the rectus is occupied by a fibrous sheet (black arrow). Also note that the fibrous sheath of the abdominal rectus muscle is less clearly visible than in the CS23 specimen due to the different staining applied (H&E). TA, transverse abdominal; IO, internal oblique; EO, external oblique, RA, abdominal rectus muscle. Scale bars: 1 mm. For 3D-PDF, see Fig. S1.

Rib development

The rib primordium had become identifiable in the 5th week of development (CS15; Verbout, 1985). The ribs were aligned in the transverse plane with the dense intervertebral disks and formed ventrolaterally oriented, stick-like extensions into the body wall and the hypaxial muscle anlagen. The remaining ventral half of the body was filled with loose mesenchyme. In CS15 and CS17 embryos (Figs2 and 3), the first seven ribs were of similar length, but the 8th–12th ribs were shorter than the first seven ribs. In CS18 embryos (Fig.4), the lateral ends of the ribs began to bend in a ventral direction and had reached the midfrontal plane. The first seven to eight ribs further increased in length, while the length of the last four ribs was progressively shorter from cranial to caudal. In the 7th week (CS20; Fig.5), the ribs had further increased in length and the first eight ribs were bending from ventral to mediocranial, that is, towards the sternal anlagen. The caudal four ribs clearly stayed behind in their ventralward development. In the 8th (CS23; Fig.6) and 9th weeks (Fig.7), the shape of the ribs did not change much anymore, but their marked approximately threefold increase in length reflected the strong increase in the circumference of the thorax and upper abdomen. In the CS15 and CS18 embryos, a small ‘rib’-like extension was present on the 7th cervical vertebra. As this description shows, comparable stages in development were reached earlier in development by the upper than the lower ribs, in agreement with a craniocaudal gradient of development.

Fig 3.

Fig 3

Open in a new tab

Bones and hypaxial muscles of the ventral body wall in a CS17 (∼ 41 days) embryo. Panels (A) (ventral view) and (B) (lateral view) show the reconstructed vertebral column, ribs, umbilical ring (UR), and genital tubercle (GT). Note the short, laterally pointing ribs and the complete absence of abdominal wall between umbilical ring (orange) and genital tubercle (pale lilac). At this stage, shoulder blades (S) could be identified. The hypaxial muscular mass of the flank is encoded red and continues cranially into that of the arm and caudally into that of the leg muscles (not shown). Panel (C), taken at the level indicated by a black line in (B), shows a histological carmine-stained section of the embryo used for this reconstruction, in which the muscular mass (red arrows) and the ribs (black arrows) can be distinguished. Scale bars: 0.2 mm. For 3D-PDF, see Fig. S1.

Fig 4.

Fig 4

Open in a new tab

Bones and hypaxial muscles of the ventral body wall in a CS18 (∼ 44 days) embryo. Panels (A–C) show ventral views of reconstructions of the vertebral column, ribs, umbilical ring (UR), muscles of the body wall and genital tubercle (GT). Note the ventralward bends in the ribs. The presternal (PS) and paired sternal bar (SB) mesenchymes are the precursors of the sternal primordium. At this stage, the shoulder blades (S) and collar bones (C) were also identifiable. The four muscles of the ventral body wall were now distinguishable and are shown separately: transverse abdominal: green; internal oblique: cyan; external oblique: red; abdominal rectus: purple. All four muscles extended caudally to the level of L1, that is, to the caudal boundary of the umbilical ring (UR). Note the lateral position of the rectus muscles and the appearance of a sheet of condensed mesenchyme (M; dark blue) between the umbilical ring cranially, the hip bones (HB) laterally, and genital tubercle (GT) caudally. The attachments of these muscles to the ribs are shown in Fig.9 C,D and Table1. Panels (D) and (E) show lateral views of the reconstruction. Panel (F), taken at the level indicated by a black line in (E), shows a carmine-stained transverse histological section of the CS18 embryo used for this reconstruction. Abdominal muscles are indicated with arrows (same color code as reconstructed muscles: green – transverse abdominal (TA), cyan – internal oblique (IO), red – external oblique (EO), purple – abdominal rectus muscle (RA). Scale bars: 0.2 mm. For 3D-PDF, see Fig. S1.

Fig 5.

Fig 5

Open in a new tab

Bones and hypaxial muscles of the ventral body wall in a CS20 (∼ 49 days) embryo. Panels (A–C) show ventral views of reconstructions of the vertebral column, ribs, umbilical ring (UR), genital tubercle (GT), sheet of condensed mesenchyme (M) and muscles of the ventral body wall. Note the increased medial bending of ribs, the formation of the sternal manubrium (MS) at the ventral tip of the 1st rib, and the extension of the sternal bars (SB) between the 2nd and 5th ribs. The attachments of the muscles to the ribs are shown in Fig.9 C,D and Table1. Note that the caudal ends of the muscles now extend along the umbilical ring (UR) towards the hip bone (HB) and have reached the level of vertebra L3 (cf. Fig.9B) and that the rectus muscles are approaching the umbilical ring. The condensed mass of mesenchyme (M) below the umbilical ring and above the genital tubercle split into a left and right portion ventromedial to the abdominal rectus muscles. In panels (D) and (E) lateral views of the reconstructions including all abdominal muscles are shown. Panel (F), taken at the level indicated by a black line in (E), shows a carmine-stained transverse histological section of the CS20 embryo used for reconstruction. The color code of the muscles and arrows is the same as in Fig.4. TA, transverse abdominal; IO, internal oblique; EO, external oblique, RA, abdominal rectus muscle. Scale bars: 0.2 mm. For 3D-PDF, see Fig. S1.

Fig 6.

Fig 6

Open in a new tab

Bones and hypaxial muscles of the ventral body wall of a CS23 (∼ 56 days) embryo. Panels (A–C) show ventral views of reconstructions of the vertebral column, ribs, umbilical ring (UR), genital tubercle (GT), muscles of the ventral body wall, and rectus sheath (RS). Note that ribs 1–7 are now attached to the sternum, meaning that they have acquired the adult configuration. The manubrium (MS) now corresponded to ribs 1 and 2, and the sternal bars (SB) to ribs 3–7. Panels (D) and (E) show lateral views of the reconstruction including the abdominal muscles and the rectus sheath. The attachments of the muscles to the ribs are shown in Fig.9 C,D and Table1. The caudal ends of the muscles are now attached to the hip bone (HB; approximately L5; cf. Fig.9B). Panel (F), taken at the level indicated by a black line in (E), shows an Azan-stained histological section of the CS23 embryo used for this reconstruction, with all muscles indicated with color-coded arrows as in Fig.4. Note that the rectus muscles had reached the boundary of the umbilical ring. Because the section was stained with Azan, the sheath of the rectus muscle is readily visible (black arrows). TA, transverse abdominal; IO, internal oblique; EO, external oblique, RA, abdominal rectus muscle. Scale bars: 0.1 mm.

Sternal development

The sternal primordium was first identifiable as a single medial or ‘presternal’ and a pair of lateral mesenchymal condensations or ‘sternal bars’ at 6.5 weeks of development (CS18; Fig.4; Chen, 1952; Engum, 2008). The presternal condensation was found above the first rib at 6.5 weeks (CS18; Fig.4) and formed the sternal manubrium in the 7th week (CS20; Fig.5). This manubrial primordium had extended to the second rib in the 8th week (CS23) embryo (Fig.6). In the 7th week (Fig.5), the paired sternal bars (Chen, 1952; Engum, 2008) had changed in position from lateral to the presternal condensation to caudal of the manubrial primordium. The medial ends of the sternal bars approached each other cranially near the ventral midline. Although the lateral parts of the sternal bars were still far apart, they already formed the medial border of the second to the fifth ribs (CS20; Fig.5). These sternal bar anlagen further extended to the seventh rib in the 8th week and began to align cranially with the manubrial primordium and fuse with each other (CS23; Fig.6). Meanwhile, the more lateral (now caudal) parts also came in close mutual contact, but were still separate entities. The fusion of the bilateral sternal bars continued in the 9th week to the level of fifth rib (Fig.7), but remained bifid more caudally until fusion was completed in the 10th week.

Formation of the intercostal and abdominal muscles

The pool of myotomal muscle precursor cells in the interlimb region increased approximately fourfold in volume between CS15 and CS17, became craniocaudally continuous between adjacent myotomes and extended ventrally beyond the ventral boundary of the vertebral bodies. At CS15 (∼ 5 weeks of development), separate epaxial and hypaxial myotomal compartments with separate dorsal and ventral spinal nerves (Fig.1C,D) had become identifiable that were still continuous via a narrow connection between the ribs (Fig.2B). The cellular arrangement of the ventrolateral lips (VLLs) of the expanding myotomes (Kalcheim & Ben-Yair, 2005) was still epithelial at CS13 and CS14 (Fig.8) and remained identifiable until CS15 (Figs2 and 8). Cranially, the interlimb hypaxial muscular band (red color code in Figs2 and 3) was continuous with that of the cervical region and the developing limb. Caudally, the muscular band extended as far as the lower boundary of the umbilical ring and was continuous with the condensed mesenchyme of the lower limb. Dorsomedially, the muscular band extended to the future transverse processes of the vertebral bodies, while it extended laterally to just beyond the tips of the ribs. Further ventrally, the body wall only contained loose mesenchyme and the umbilical veins and their tributaries.

Fig 8.

Fig 8

Open in a new tab

Position of the ventrolateral lip of the dermomyotome in human embryos at 4–9 weeks of development. Panel (A) illustrates the expansion of the ventrolateral lips (VLLs) of the dermomyotome in the lateral body wall relative to the notochord, at the level of the umbilical orifice as a function of age. Panels (B–D) show histological sections of CS13 (∼ 32 days, carmine-stained, taken at level of C6), CS14 (∼ 34 days, H&E-stained, taken at level of Th1), and CS15 embryos (∼ 36 days, H&A-stained, taken at level of Th10), respectively. The position of the VLL is indicated by arrows. A circle was drawn through the notochord and VLLs of the left and right dermomyotomes. The position of the radius through the VLL relative to that through the notochord was then measured (shown in panel C). The data were fitted with a 3rd degree polynomial function (R2 = 0.95). Scale bars: 0.1 mm.

The differentiation of the single band of hypaxial muscle into separate layers became apparent at the end of the 6th week (CS18; Figs4 and 9). Ab initio, three separate muscle sheets were identifiable. Based on their position in subsequent stages, these muscles corresponded with the external oblique (outer sheet), internal oblique (middle sheet) and transverse abdominal muscles (inner sheet), and extended cranially from ribs 5, 7, and 2, respectively, to the level of the 1st lumbar vertebra caudally, where all three layers ended (Figs4 and 9). In addition, a single longitudinal muscle was identifiable at the lateral border of the three muscle sheets, which extended from rib 5 to the level of the 1st lumbar vertebra and corresponded with the abdominal rectus muscle (Figs4 and 9). Cranially, the lateral abdominal muscles were continuous with the intercostal muscles of the thorax, and their caudal boundary corresponded with the caudal boundary of the umbilical cord.

Fig 9.

Fig 9

Open in a new tab

Appearance of the infraumbilical region and craniocaudal extension of muscles. Panel (A) shows the increasing distance between the umbilical ring and the genital tubercle between 7 and 9 weeks of development. The trend line was fitted with a 3rd degree polynomial function. Panel (B) shows the coincident caudal extension of the caudal boundaries of all abdominal muscles in the same time period. The data shown in panels (A) and (B) reflect the formation of the infraumbilical region. Panels (C) and (D) show the descent of the cranial attachment of the abdominal muscles between 6.5 and 8 weeks of development (transverse abdominal: green diamonds; abdominal rectus: purple circles; internal oblique: cyan diamonds; external oblique: red circles). The trend lines in panels (B–D) were fitted with 2nd degree polynomial functions.

Up to CS18, the infraumbilical region remained non-existent. The umbilical cord and the developing genital tubercle still shared part of their adjacent boundaries at CS15 (Fig.2) but had become separate identities at CS17 (Fig.3). At CS18 a dense mesenchymal band began to develop between the midline ventrally, and the developing hip bone and dorsal mesenchyme cranial to the hip bone dorsolaterally (Fig.4). In CS20, the dense mesenchyme below the umbilicus was still identifiable but had split up ventromedially to surround the abdominal rectus muscles (Fig.5). The distance between the umbilicus and genital tubercle, still adjacent structures at 6 weeks (CS17), rapidly increased in the next weeks to reach a temporary plateau at 9 weeks (Fig.9A). Simultaneously, the caudal boundaries of the muscles extended two segments (to L3) in the 7th week (CS20; Figs5 and 9B) and two more segments (to L5) in the 8th week to reach the cranial boundary of the hip bone (CS23; Figs6 and 9B). Concurrent with the infraumbilical expansion of the abdominal muscles, the cranial attachments of the internal and external obliques and rectus muscles descended two segments, and that of transverse abdominal, in its most ventrolateral part, descended six segments to attain their definitive cranial attachments at ribs 6, 9, 8, and 7 (external, internal, transverse and rectus abdominals, respectively; Fig.9C,D). In addition, the most ventral boundary of the muscles changed from lateral (CS18; Fig.4) via ventrolateral (CS20; Fig.5) to ventromedial (CS23; Fig.6). As a result, the abdominal rectus muscle reached the umbilical ring in the 9th week (Fig.7) but its left and right parts were still quite far apart because of the intervening physiological hernia of the intestines. The aponeurotic part of the external abdominal and the thick fibrous sheath enveloping the abdominal rectus muscle were visible from the 8th week onwards (Figs6 and 7). Of interest, the aponeurosis appeared thickest on the ventral side of the rectus muscle.

In summary, the initially single ‘band’ of body wall muscles expanded ventrally but not caudally until it differentiated into the three layers that characterize the intercostal and abdominal muscles and the abdominal rectus muscle at CS18 (6.5 weeks). The infraumbilical region and the muscles occupying it only started to expand thereafter, with a burst in growth between 6.5 and 8 weeks of development (CS18–CS23) (Fig.9). Coincident with the expansion of the infraumbilical region, both the cranial and the caudal attachments of the abdominal muscles descended several segments relative to the vertebral column (Table1). In addition to descending caudally, the ventral boundary of the muscles acquired a more and more medial position, with the abdominal rectus touching the lateral rim of the umbilical orifice at 9 weeks.

Table 1.

Cranial and caudal attachments of the anterior abdominal wall muscles

Stage/attachment Abdominal rectus Transverse abdominis External oblique Internal oblique
Cranial Caudal Cranial Caudal Cranial Caudal Cranial Caudal
6.5th week (CS 18) Th5 L1 Th2 L1 Th5 L1 Th7 L1
7th week (CS 20) Th7 L3 Th6 L3 Th6 L3 Th9 L3
8th week (CS 23) Th6 L5 Th8 L5 Th6 L5 Th9 L5
9th week Th6 L5 Th8 L5 Th6 L5 Th9 L5
Total descent 1 4 6 4 1 4 2 4
Open in a new tab

The closure of the umbilical hernia

Both rectus muscles were found laterally in the body wall, becoming first identifiable at CS18. We measured the distance on the ventral body wall between the left and right rectus muscles (‘diastasis’) at the level of the umbilicus. The distance declined non-significantly from ∼ 5 mm at 6 weeks of development to ∼ 3 mm at 9 weeks of development (Fig.10A; P = 0.57), whereas the diameter of the umbilical ring increased, also non-significantly, from ∼ 1 to 2 mm in this period (Fig.10B; P = 0.34). Meanwhile, the body circumference at the level of the umbilicus increased approximately threefold, significantly, from ∼ 6 to 18 mm (Fig.10C; P = 0.006). As a result, the fraction of the body circumference that was not covered by muscle, declined continuously with time between 6 and 10 weeks of development (approximately fivefold; P = 0.001; Fig.10D). Furthermore, the rectus muscles began to surround the umbilical ring more and more tightly (Fig.10E; P = 0.014). These data show that the withdrawal of the midgut from the physiological hernia in the 9th week (Kim et al. 2003) coincides with the occlusion of the hernia sac between the rectus muscles.

Fig 10.

Fig 10

Open in a new tab

The distance between both abdominal rectus muscles and the diameter of the umbilical ring are inversely correlated. Panel (A) shows that the distance between the medial boundaries of both abdominal rectus muscles (‘diastasis’) declines only slightly and not significantly with development (∼ 0.08 mm day−1; P = 0.57). Similarly, the diameter of the umbilical ring increases only slowly and non-significantly (∼ 0.04 mm day−1; P = 0.34; panel B). Panel (C) shows that the body circumference of the embryo at the level of the umbilicus increases ∼ 0.5 mm day−1 between 6 and 10 weeks of development (P = 0.006). Panel (D) shows the pronounced decrease of the ‘diastasis’ of the rectus muscles as a fraction of the body circumference at the umbilical level. The trend line was fitted with a 2nd degree polynomial function (P = 0.001). The most pronounced relative decline occurred between 6 and 8 weeks (∼ 4% per day). Panel (E) shows that the ratio of the diameter of the umbilical ring and the ‘diastasis’ of the abdominal rectus muscles approaches unity with 1.7% per day (P = 0.014). The data show that the ‘diastasis’ and the diameter of the umbilical ring hardly change with development, whereas the body circumference grows approximately threefold faster. As a result, the umbilical hernia becomes shut in by the muscles of the ventral body wall. Note that the structures that form part of the umbilical ring explain that the ratio is ‘only’ 70% at 10 weeks (70 days) (cf. Fig.10E).

Discussion

Relative to the vertebrae and ribs, the primordia of the sternum and abdominal wall muscles appeared laterally in the ventral body wall of CS15–18 embryos and expanded in a ventrolateral direction. The intercostal and all abdominal wall muscles became identifiable as separate entities from the common myotomal band at the transition of CS17–CS18 (6–6.5 weeks of development). In the subsequent stages, the rib, sternal, and muscle primordia extended ventromedially and caudally, with the bilateral sternal bars beginning to fuse in the midline between CS20 and CS23 (8th week) and the rectus muscles reaching the umbilicus at CS23 (8 weeks of development).

Proposed model: mediolateral growth in the dorsolateral body wall

A key finding in this study was that the absolute distance between the right- and left-sided rectus muscles (‘diastasis’) hardly changed across the stages studied, but decreased approximately fivefold relative to the body circumference at the umbilical level between 6 and 10 weeks of development. Figure11 shows these changes in a schematic drawing. In most illustrations, the increasing size of embryos with age is downsized so that all depicted stages have a similar size. In such visualizations, the ribs and muscles have to migrate through the body wall to reach the ventral midline (arrows in Fig.11A; Munger & Munger, 1991; Hirano et al. 2006; Yang et al. 2012). Migratory failure is the most common explanation for ventral body wall defects and persisting umbilical hernia (Brewer & Williams, 2004; Engum, 2008; Feldkamp et al. 2011). In reality, however, the part of the ventral body wall that does not contain bone and muscle decreases slightly in width, whereas the part of the body wall that does contain bone and muscle increases approximately threefold in circumference. We, therefore, postulate that the expansion due to mediolateral growth in the dorsolateral body wall of the embryo is quantitatively more important for the formation of the osseous and muscular ventromedial part of the ventral body wall than cell migration. Similarly, differential growth in the dorsolateral part of the body appears to be responsible for processes, thus far explained by cell migration, such as sclerotome formation from the somite, spinal ganglion and sympathetic trunk formation from the neural crest, and thyroid, parathyroid, and thymus gland formation from the pharyngeal pouches (Smits-Van Prooije et al. 1988; Gasser, 2006).

Fig 11.

Fig 11

Open in a new tab

Model for the closure of the ventral body wall. Panel (A) shows the classical model with the migration of ribs and muscles through the body wall in a ventral direction (arrows). In panel (B) the proposed new model shows that the robust increase in body size of the embryo contrasts with the minimal changes in size of the umbilical ring and ‘diastasis’ of the rectus muscles. The growth of the body occurs mainly in its dorso-lateral parts (double-headed arrow).

Ventrocaudal extension of sternum, ribs, and muscles

The early development of the abdominal muscles in mammals is similar to that in the avian embryo (Christ et al. 1983). Our description of the changes in position of the sternal anlagen or ‘bands’ in human embryos between CS18 and CS20 corresponds with that provided by Chen (1952) in the rodent. Both Chen (1953) and his mentor Fell (1939) concluded that the ventrocaudal change in position of the sternal anlagen coincided with and might even be caused by a descent of ventral organs and the body wall. The anlagen of the abdominal rectus muscle are also known as the ‘abdominal bands’ and have been interpreted as caudal extensions of the sternal bands (Munger & Munger, 1991). Up to approximately CS17 [6th week in the human embryo and E13.5 in rodents (Munger & Munger, 1991)], the umbilicus and genital tubercle were still adjacent structures and the caudal boundary of the developing muscles coincided with the caudal boundary of the umbilical cord. As the muscles gradually expanded ventrally and caudally to form the infraumbilical region during the 7th and 8th weeks of development, Munger & Munger (1991) observed as their ‘most unusual finding’ that the (cutaneous branches of the) spinal nerves co-migrated with the abdominal muscles. This finding shows that the ventrocaudal course of these nerves in the adult reveals the direction of growth of the body wall in the embryo.

The ‘lateral somitic frontier’: migration or expansion

The abdominal wall muscles that change most in position all belong to the abaxial group and are, therefore, surrounded by cells of the lateral plate mesoderm. At first sight, our conclusion that the ventral body wall expands ventrally by local growth in the dorsolateral body region (Fig.11) and convincing literature data that the somitic muscle cells of the abdominal muscles become enveloped by lateral plate-derived cells [the ‘lateral somitic frontier’ concept (Nowicki et al. 2003; Durland et al. 2008; Shearman & Burke, 2009)] seem to be at odds. This is because the ‘differential growth model’ that we and others (Vermeij-Keers et al. 1996; Gasser, 2006) advocate posits that cell migration is not necessary for new structures to develop, whereas the lateral somitic frontier concept states that somitic muscle cells migrate or translocate into the lateral plate area. In considering this paradox, it should be kept in mind that interactions between myoblasts/myocytes and the extracellular matrix play a crucial role in skeletal muscle development (for reviews see Krauss, 2010; Thorsteinsdottir et al. 2011; Goody et al. 2015) and that the balance of cell–cell and cell–matrix adhesive interactions determines the outcome of the morphogenetic event (Singh et al. 2015). In fact, the abdominal muscles of children with the ‘Prune belly’ syndrome are present at the proper localization, but the muscle cells have a scattered distribution, in particular in the ventral, infraumbilical area, whereas the mediodorsal portion shows nearly normal muscle and fascial layers (Afifi et al. 1972; Shimada et al. 2000; Tonni et al. 2013). We, therefore, hypothesize that this as yet unexplained abdominal wall syndrome is caused by an imbalance between cell–cell and cell–matrix interactions.

Implications for malformations

Overall, ventral body wall defects occur in approximately 1 : 2000 live births (Gibbin et al. 2003). Within this group, gastroschisis and omphalocele, including thoracoabdominoschisis, are most prevalent with frequencies of 1 : 2–4000 (Glasser, 2001), whereas other ventral midline defects, such as ectopia cordis, exstrophy-epispadias complex (bladder or cloacal exstrophy), or a combination of a ventral body wall and a limb defect are at least 10-fold rarer (Glasser, 2001; Hunter et al. 2011). In omphalocele and gastroschisis, the rectus muscle was intact but inserted more laterally on the costal margins and xiphoid process, respectively (Klein & Hertzler, 1981; Nichol et al. 2012). In the same way, the sternum in ectopia cordis is usually accompanied by a bifid sternum, diastasis of the abdominal rectus muscles, and a diaphragmatic defect (Kanagasuntheram & Verzin, 1962). Recent studies on bladder or cloacal exstrophy have also shown that the abdominal muscles were present and attached to the pubic bones, even though the pubic bones were widely separated (Feldkamp et al. 2011; Siffel et al. 2011). Taken together, these observations strongly support the concept that the bones and ventral body wall muscles may have undergone normal differentiation but have not sufficiently expanded ventromedially. We, therefore, hypothesize that each of these ventral midline defects have their origin in insufficient dorsoventral growth (cf. Fig.10).

Acknowledgments

We thank Drs Maurice van den Hoff (AMC) and Marco de Ruiter (LUMC) for allowing us to use their institutional series of human embryos. Additional embryos came from the Virtual Human Embryo project (Dr. John Cork; Cell Biology & Anatomy, LSU Health Sciences Center, New Orleans; http://virtualhumanembryo.lsuhsc.edu), who made digitized sections available to us. Further, special thanks go to Onne Ronda for his help in making some of the body wall reconstructions and Els Terwindt (MU) for technical assistance.

Author contributions

HM participated in collection, analysis and interpretation of data, and wrote and edited the manuscript. JH made substantial contributions to the collection, analysis, interpretation, and rendering of data. GM was responsible for the reconstructions of the vertebral columns. SEK participated in analysis of data, provided guidance, assisted with data interpretation, and edited the manuscript. WL conceived the study, provided guidance and assisted with data interpretation, and helped write and edit the manuscript.

Supporting Information

Additional Supporting Information may be found in the online version of this article:

Figure S1. Interactive 3D pdfs of the ventral body wall structures in human embryos at CS15, CS17, CS18, CS20, CS23 and 9 weeks of development, respectively.

joa0227-0673-sd1.pdf (45.6MB, pdf)

References

  1. Afifi AK, Rebeiz J, Mire J. The myopathology of the Prune belly syndrome. J Neurol Sci. 1972;15:153–165. doi: 10.1016/0022-510x(72)90003-2. , et al. ( [DOI] [PubMed] [Google Scholar]
  2. Blaas HG, Eik-Nes SH. Sonoembryology and early prenatal diagnosis of neural anomalies. Prenat Diagn. 2009;29:312–325. doi: 10.1002/pd.2170. [DOI] [PubMed] [Google Scholar]
  3. Bothe I, Ahmed MU, Winterbottom FL. Extrinsic versus intrinsic cues in avian paraxial mesoderm patterning and differentiation. Dev Dyn. 2007;236:2397–2409. doi: 10.1002/dvdy.21241. , et al. ( [DOI] [PubMed] [Google Scholar]
  4. Brewer S, Williams T. Finally, a sense of closure? Animal models of human ventral body wall defects. BioEssays. 2004;26:1307–1321. doi: 10.1002/bies.20137. [DOI] [PubMed] [Google Scholar]
  5. Buchholtz EA. Crossing the frontier: a hypothesis for the origins of meristic constraint in mammalian axial patterning. Zoology (Jena) 2014;117:64–69. doi: 10.1016/j.zool.2013.09.001. [DOI] [PubMed] [Google Scholar]
  6. Buckingham M, Bajard L, Chang T. The formation of skeletal muscle: from somite to limb. J Anat. 2003;202:59–68. doi: 10.1046/j.1469-7580.2003.00139.x. , et al. ( [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen JM. Studies on the morphogenesis of the mouse sternum. I. Normal embryonic development. J Anat. 1952;86:373–386. [PMC free article] [PubMed] [Google Scholar]
  8. Chen JM. Studies on the morphogenesis of the mouse sternum. III. Experiments on the closure and segmentation of the sternal bands. J Anat. 1953;87:130–149. [PMC free article] [PubMed] [Google Scholar]
  9. Chevallier A. Role of the somitic mesoderm in the development of the thorax in bird embryos. II. Origin of thoracic and appendicular musculature. J Embryol Exp Morphol. 1979;49:73–88. [PubMed] [Google Scholar]
  10. Christ B, Jacob M, Jacob HJ. On the origin and development of the ventrolateral abdominal muscles in the avian embryo. An experimental and ultrastructural study. Anat Embryol (Berl) 1983;166:87–101. doi: 10.1007/BF00317946. [DOI] [PubMed] [Google Scholar]
  11. Corner GW. A Well-Preserved Human Embryo of 10 Somites. Washington, DC: Carnegie Institute of Washington; 1929. [Google Scholar]
  12. Deries M, Collins JJ, Duxson zMJ. The mammalian myotome: a muscle with no innervation. Evol Dev. 2008;10:746–755. doi: 10.1111/j.1525-142X.2008.00289.x. [DOI] [PubMed] [Google Scholar]
  13. Dietrich S, Schubert FR, Healy C. Specification of the hypaxial musculature. Development. 1998;125:2235–2249. doi: 10.1242/dev.125.12.2235. , et al. ( [DOI] [PubMed] [Google Scholar]
  14. Durland JL, Sferlazzo M, Logan M. Visualizing the lateral somitic frontier in the Prx1Cre transgenic mouse. J Anat. 2008;212:590–602. doi: 10.1111/j.1469-7580.2008.00879.x. , et al. ( [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Engum SA. Embryology, sternal clefts, ectopia cordis, and Cantrell's pentalogy. Semin Pediatr Surg. 2008;17:154–160. doi: 10.1053/j.sempedsurg.2008.03.004. [DOI] [PubMed] [Google Scholar]
  16. Evans DJ, Valasek P, Schmidt C. Skeletal muscle translocation in vertebrates. Anat Embryol (Berl) 2006;211(Suppl 1):43–50. doi: 10.1007/s00429-006-0121-1. , et al. ( [DOI] [PubMed] [Google Scholar]
  17. Feldkamp ML, Botto LD, Amar E. Cloacal exstrophy: an epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research. Am J Med Genet C Semin Med Genet. 2011;157C:333–343. doi: 10.1002/ajmg.c.30317. , et al. (. . [DOI] [PubMed] [Google Scholar]
  18. Fell HB. The origin and developmental mechanics of the avian sternum. Philos Trans R Soc Lond B Biol Sci. 1939;229:407–463. [Google Scholar]
  19. Furst DO, Osborn M, Weber K. Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly. J Cell Biol. 1989;109:517–527. doi: 10.1083/jcb.109.2.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gasser RF. Evidence that some events of mammalian embryogenesis can result from differential growth, making migration unnecessary. Anat Rec B New Anat. 2006;289:53–63. doi: 10.1002/ar.b.20092. [DOI] [PubMed] [Google Scholar]
  21. Gibbin C, Touch S, Broth RE. Abdominal wall defects and congenital heart disease. Ultrasound Obstet Gynecol. 2003;21:334–337. doi: 10.1002/uog.93. , et al. ( [DOI] [PubMed] [Google Scholar]
  22. Glasser J. eMedicine. 2001. Omphalocele and gastroschisis http://www.emedicine.com/ (accessed 25 November 2014)
  23. Goody MF, Sher RB, Henry CA. Hanging on for the ride: adhesion to the extracellular matrix mediates cellular responses in skeletal muscle morphogenesis and disease. Dev Biol. 2015;401:75–91. doi: 10.1016/j.ydbio.2015.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hassett S, Smith GH, Holland AJ. Prune belly syndrome. Pediatr Surg Int. 2012;28:219–228. doi: 10.1007/s00383-011-3046-6. [DOI] [PubMed] [Google Scholar]
  25. Hirano M, Kiyonari H, Inoue A. A new serine/threonine protein kinase, Omphk1, essential to ventral body wall formation. Dev Dyn. 2006;235:2229–2237. doi: 10.1002/dvdy.20823. , et al. ( [DOI] [PubMed] [Google Scholar]
  26. Hunter AG, Seaver LH, Stevenson RE. Limb-body wall defect. Is there a defensible hypothesis and can it explain all the associated anomalies? Am J Med Genet A. 2011;155A:2045–2059. doi: 10.1002/ajmg.a.34161. [DOI] [PubMed] [Google Scholar]
  27. Iimura T, Denans N, Pourquie O. Establishment of Hox vertebral identities in the embryonic spine precursors. Curr Top Dev Biol. 2009;88:201–234. doi: 10.1016/S0070-2153(09)88007-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kalcheim C, Ben-Yair R. Cell rearrangements during development of the somite and its derivatives. Curr Opin Genet Dev. 2005;15:371–380. doi: 10.1016/j.gde.2005.05.004. [DOI] [PubMed] [Google Scholar]
  29. Kanagasuntheram R, Verzin JA. Ectopia cordis in man. Thorax. 1962;17:159–167. doi: 10.1136/thx.17.2.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kim WK, Kim H, Ahn DH. Timetable for intestinal rotation in staged human embryos and fetuses. Birth Defects Res A Clin Mol Teratol. 2003;67:941–945. doi: 10.1002/bdra.10094. , et al. ( [DOI] [PubMed] [Google Scholar]
  31. Klein MD, Hertzler JH. Congenital defects of the abdominal wall. Surg Gynecol Obstet. 1981;152:805–808. [PubMed] [Google Scholar]
  32. Krauss RS. Regulation of promyogenic signal transduction by cell-cell contact and adhesion. Exp Cell Res. 2010;316:3042–3049. doi: 10.1016/j.yexcr.2010.05.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Loughna P, Chitty L, Evans T. Fetal size and dating: charts recommended for clinical obstetric practice. Ultrasound Med Biol. 2009;17:160–166. , et al. ( [Google Scholar]
  34. Monsoro-Burq AH. Sclerotome development and morphogenesis: when experimental embryology meets genetics. Int J Dev Biol. 2005;49:301–308. doi: 10.1387/ijdb.041953am. [DOI] [PubMed] [Google Scholar]
  35. Munger GT, Munger BL. Differentiation of the anterior body wall and truncal epidermis and associated co-migration of cutaneous nerves and mesenchyme. Anat Rec. 1991;231:261–274. doi: 10.1002/ar.1092310214. [DOI] [PubMed] [Google Scholar]
  36. Nichol PF, Corliss RF, Yamada S. Muscle patterning in mouse and human abdominal wall development and omphalocele specimens of humans. Anat Rec (Hoboken) 2012;295:2129–2140. doi: 10.1002/ar.22556. , et al. ( [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nowicki JL, Burke AC. Hox genes and morphological identity: axial versus lateral patterning in the vertebrate mesoderm. Development. 2000;127:4265–4275. doi: 10.1242/dev.127.19.4265. [DOI] [PubMed] [Google Scholar]
  38. Nowicki JL, Takimoto R, Burke AC. The lateral somitic frontier: dorso-ventral aspects of anterio-posterior regionalization in avian embryos. Mech Dev. 2003;120:227–240. doi: 10.1016/s0925-4773(02)00415-x. [DOI] [PubMed] [Google Scholar]
  39. O'Rahilly R, Muller F. Somites, spinal ganglia, and centra. Enumeration and interrelationships in staged human embryos, and implications for neural tube defects. Cells Tissues Organs. 2003;173:75–92. doi: 10.1159/000068948. [DOI] [PubMed] [Google Scholar]
  40. O'Rahilly R, Muller F. Developmental stages in human embryos: revised and new measurements. Cells Tissues Organs. 2010;192:73–84. doi: 10.1159/000289817. [DOI] [PubMed] [Google Scholar]
  41. O'Rahilly R, Müller F. Developmental Stages of Human Embryos, Including a Revision of Streeter's ‘Horizons’ and a Survey of the Carnegie Collection. Washington, DC: Carnegie Institute of Washington; 1987. [Google Scholar]
  42. Ordahl CP, Le Douarin NM. Two myogenic lineages within the developing somite. Development. 1992;114:339–353. doi: 10.1242/dev.114.2.339. [DOI] [PubMed] [Google Scholar]
  43. Pooh RK, Shiota K, Kurjak A. Imaging of the human embryo with magnetic resonance imaging microscopy and high-resolution transvaginal 3-dimensional sonography: human embryology in the 21st century. Am J Obstet Gynecol. 2011;204:77.e1–77.e16. doi: 10.1016/j.ajog.2010.07.028. [DOI] [PubMed] [Google Scholar]
  44. Sacks LD, Cann GM, Nikovits W., Jr Regulation of myosin expression during myotome formation. Development. 2003;130:3391–3402. doi: 10.1242/dev.00541. , et al. ( [DOI] [PubMed] [Google Scholar]
  45. Shearman RM, Burke AC. The lateral somitic frontier in ontogeny and phylogeny. J Exp Zool B Mol Dev Evol. 2009;312:603–612. doi: 10.1002/jez.b.21246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shimada K, Hosokawa S, Tohda A. Histology of the fetal prune belly syndrome with reference to the efficacy of prenatal decompression. Int J Urol. 2000;7:161–166. doi: 10.1046/j.1442-2042.2000.00159.x. , et al. ( [DOI] [PubMed] [Google Scholar]
  47. Siffel C, Correa A, Amar E. Bladder exstrophy: an epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research, and an overview of the literature. Am J Med Genet C Semin Med Genet. 2011;157C:321–332. doi: 10.1002/ajmg.c.30316. , et al. ( [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Singh J, Hussain F, Decuzzi P. Role of differential adhesion in cell cluster evolution: from vasculogenesis to cancer metastasis. Comput Methods Biomech Biomed Engin. 2015;18:282–292. doi: 10.1080/10255842.2013.792917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Smits-Van Prooije AE, Vermeij-Keers C, Poelmann RE. The formation of mesoderm and mesectoderm in 5- to 41-somite rat embryos cultured in vitro, using WGA-Au as a marker. Anat Embryol (Berl) 1988;177:245–256. doi: 10.1007/BF00321135. , et al. ( [DOI] [PubMed] [Google Scholar]
  50. Taylor JR. Growth of human intervertebral discs and vertebral bodies. J Anat. 1975;120:49–68. [PMC free article] [PubMed] [Google Scholar]
  51. Thorsteinsdottir S, Deries M, Cachaco AS. The extracellular matrix dimension of skeletal muscle development. Dev Biol. 2011;354:191–207. doi: 10.1016/j.ydbio.2011.03.015. , et al. ( [DOI] [PubMed] [Google Scholar]
  52. Tonni G, Ida V, Alessandro V. Prune-belly syndrome: case series and review of the literature regarding early prenatal diagnosis, epidemiology, genetic factors, treatment, and prognosis. Fetal Pediatr Pathol. 2013;31:13–24. doi: 10.3109/15513815.2012.659411. , et al. ( [DOI] [PubMed] [Google Scholar]
  53. Vasyutina E, Birchmeier C. The development of migrating muscle precursor cells. Anat Embryol (Berl) 2006;211(Suppl 1):37–41. doi: 10.1007/s00429-006-0118-9. [DOI] [PubMed] [Google Scholar]
  54. Verbout AJ. The development of the vertebral column. Adv Anat Embryol Cell Biol. 1985;90:1–122. doi: 10.1007/978-3-642-69983-2. [DOI] [PubMed] [Google Scholar]
  55. Vermeij-Keers C, Hartwig NG, Van Der Werff JF. Embryonic development of the ventral body wall and its congenital malformations. Semin Pediatr Surg. 1996;5:82–89. [PubMed] [Google Scholar]
  56. Wachtler F, Christ B. The basic embryology of skeletal muscle formation in vertebrates: the avian model. Semin Dev Biol. 1992;3:217–227. [Google Scholar]
  57. Wessels A, Vermeulen JL, Viragh S. Spatial distribution of ‘tissue-specific’ antigens in the developing human heart and skeletal muscle. I. An immunohistochemical analysis of creatine kinase isoenzyme expression patterns. Anat Rec. 1990;228:163–176. doi: 10.1002/ar.1092280208. , et al. ( [DOI] [PubMed] [Google Scholar]
  58. Wessels A, Vermeulen JL, Viragh S. Spatial distribution of ‘tissue-specific’ antigens in the developing human heart and skeletal muscle. II. An immunohistochemical analysis of myosin heavy chain isoform expression patterns in the embryonic heart. Anat Rec. 1991;229:355–368. doi: 10.1002/ar.1092290309. , et al. ( [DOI] [PubMed] [Google Scholar]
  59. Wisser J, Dirschedl P, Krone S. Estimation of gestational age by transvaginal sonographic measurement of greatest embryonic length in dated human embryos. Ultrasound Obstet Gynecol. 1994;4:457–462. doi: 10.1046/j.1469-0705.1994.04060457.x. [DOI] [PubMed] [Google Scholar]
  60. Yang JD, Hwang HP, Kim JH. Development of the rectus abdominis and its sheath in the human fetus. Yonsei Med J. 2012;53:1028–1035. doi: 10.3349/ymj.2012.53.5.1028. , et al. ( [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Figure S1. Interactive 3D pdfs of the ventral body wall structures in human embryos at CS15, CS17, CS18, CS20, CS23 and 9 weeks of development, respectively.

joa0227-0673-sd1.pdf (45.6MB, pdf)

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

RESOURCES