FIGURE 1.

The cranial base and synchondroses. (A) Ventral view of bone staining of the mouse cranial base at postnatal day (P) 0. The middle line of the cranial base is formed by the presphenoid, basisphenoid (BS), and basioccipital (BO) bones. Between the mineralized bones, there are two cartilaginous synchondroses, the intersphenoid synchondrosis (ISS) and the spheno-occipital synchondrosis (SOS). Please note that the presphenoid bone is invisible because of the palatine process (PA). AT, ala temporalis (greater wing) of the basisphenoid bone; CA, canalicular part of auditory capsule; EO, exoccipital bone; FB, facial bone; IOSA, intraoccipital synchondrosis; SAB, synchondrosis, alar-basisphenoidalis; SES, spheno-ethmoidal synchondrosis. (B) Safranin-O staining of the mouse cranial base at embryonic day (E) 16.5. The presphenoid (PS), basisphenoid (BS), and basioccipital (BO) bones are separated by two synchondroses, the intersphenoid synchondrosis (ISS) and spheno-occipital synchondrosis (SOS). The synchondrosis is composed of bipolar growth plates with a central resting (r), proliferating (p), and prehypertrophic (ph) zones. PA, palate; Rp, Rathke’s pouch. (C) Schematic illustration of the tissue origins of the cranial base derived from the neural crest shown in red and those derived from the mesoderm in blue (McBratney-Owen et al., 2008). BS, basisphenoid bone; BO, basioccipital bone; EO, exoccipital bone; PS, presphenoid bone. (D) STRING protein-protein interaction network of mouse genes involved in abnormal synchondroses. The network was constructed using the STRING tool³, with mouse genes involved in abnormal synchondroses (Table 1) used as input. Different colors represent different kinds of evidence of connection between proteins. (E) (a) Skulls from wild-type and Tbx1-deficient mice at birth were analyzed by micro-computed tomography and are shown in a “bird’s eye view.” In Tbx1-deficient mice, the spheno-occipital synchondrosis (SOS) was completely mineralized (Funato et al., 2020). BO, basioccipital bone; BS, basisphenoid bone; ISS, intersphenoid synchondrosis; PA, palatine process. (b) A predicted model for TBX1-mediated regulation of endochondral ossification of SOS. By inhibiting the activity of RUNX2 and the expression of RUNX2 target genes, TBX1 negatively regulates chondrocyte differentiation as well as subsequent endochondral ossification in the SOS.