Figure 2.

Early neurogenesis in the vertebrate embryo. (A) Lateral surface view of amphibian embryo after gastrulation. Dorsal neuroectoderm (neural plate; purple) gives rise to the brain (anterior neural plate, left) and spinal cord (posterior neural plate, right). (B-D) Cross section of neural plate (B) and neural tube (C). (D1, D2) depict enlarged subsections of neuroepithelium at an early phase (D1) and later phase (D2) of progenitor cell proliferation. The vertebrate neuroectoderm remains configured as a layer of neuroepithelial progenitors surrounding an inner lumen (ventricle). Progenitors initially divide symmetrically, resulting in an expansion of the neuroepithelium (D1). During a later phase, asymmetric (neurogenic) divisions generate primary neurons which delaminate from the ventricular layer (D2), whereas other daughter cells remain at the ventricular surface to continue dividing. (E-G) Small clones of primary neurons (E, F) and neuroepithelial progenitors (G) in Xenopus (E, G; from Hartenstein, 1989, with permission) and zebrafish (F; from Papan and Campos-Ortega, 1997, with permission) labeled by dye injection into individual cells at neural plate stage. (H1–4) Neural proliferation in mouse. Schematic cross sections of neuroepithelium at different stages of development. Early divisions of neural progenitors are symmetric, resulting in a great expansion of the neural tube (H2; prior to E10.5). Between E10.5 and E12.5, neurogenic mitotic activity commences (H3). Individual progenitors, now called apical radial glia (aRG), undergo a series of asymmetric divisions that give rise to 8–9 neural precursors and/or intermediate progenitors (H4; around E16.5). These cells remain in close contact and form an ontogenetic column (see also Fig.5C, D). Intermediate progenitors form the subventricular zone (SVZ). In mouse, these cells typically undergo only one more terminal division. Notch/Delta signaling promotes the fate of ventricular epithelial progenitors, as opposed to neural precursors or intermediate progenitors (inset in H2/3). (I1–2) In large mammals (e.g., primates) with folded cortex the subventricular zone splits into an inner and outer subventricular zone (iSVZ and oSVZ), respectively. Neural progenitors of the ventricular layer lose contact to the pial surface (“truncated radial glia”, tRG); progenitors of the oVZ (“basal radial glia”, bRG) continue to divide for an extended period, producing predominantly neurons of superficial cortical layers (from Nowakowski et al., 2016, with permission). (J1–4) Neurogenesis in the dorsal forebrain of different vertebrate clades (J1: reptiles, amphibians, fishes; J2: birds; J3: rodents; J4: primates; from Cardenas and Borrell, 2019, with permission). In anamniotes and reptiles, epithelial progenitors of the ventricular layer (apical radial glia; blue) directly give rise to postmitotic neural precursors (red) which form a basal neural layer (NL; “direct neurogenesis”). In birds, apical radial glia not only give rise to neural precursors, but also to mitotically active intermediate progenitors (magenta) which populate a subventricular zone (SVZ; “indirect neurogenesis”). This mode of indirect neurogenesis accounts for an increased number of neurons generated from the neuroepithelium. Indirect neurogenesis is even more pronounced in mammals, where neurons form a multilayered cortical plate (CP). Large mammals with a gryrated cortex show a dramatic expansion of intermediate neural progenitors, forming an inner and inner (iSVZ) and outer subventricular zone (oSVZ).