Distinct spatiotemporal roles of hedgehog signalling during chick and mouse cranial base and axial skeleton development

Abstract

The cranial base exerts a supportive role for the brain and includes the occipital, sphenoid and ethmoid bones that arise from cartilaginous precursors in the early embryo. As the occipital bone and the posterior part of the sphenoid are mesoderm derivatives that arise in close proximity to the notochord and floor plate, it has been assumed that their development, like the axial skeleton, is dependent on Sonic hedgehog (Shh) and modulation of bone morphogenetic protein (Bmp) signalling. Here we examined the development of the cranial base in chick and mouse embryos to compare the molecular signals that are required for chondrogenic induction in the trunk and head. We found that Shh signalling is required but the molecular network controlling cranial base development is distinct from that in the trunk. In the absence of Shh, the presumptive cranial base did not undergo chondrogenic commitment as determined by the loss of Sox9 expression and there was a decrease in cell survival. In contrast, induction of the otic capsule occurred normally demonstrating that induction of the cranial base is uncoupled from formation of the sensory capsules. Lastly, we found that the early cranial mesoderm is refractory to Shh signalling, likely accounting for why development of the cranial base occurs after the axial skeleton. Our data reveal that cranial and axial skeletal induction is controlled by conserved, yet spatiotemporally distinct mechanisms that co-ordinate development of the cranial base with that of the cranial musculature and the pharyngeal arches.

The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling

“…Its position at three important tissue boundaries [10] exposes this region to numerous signaling pathways involved in cranial base morphogenesis, such as Shh [11]. Shh is in fact secreted both by the rostral tip of the notochord [11,12] and the most rostral zone of the foregut endoderm [13]. While the positions of the RP relative to the rostral end of the notochord and to the posterior border of the neural crest-derived tissues are well documented, there prevails an uncertainty about its position in relation to the gut endoderm [14,15].…”

The Ptch1DL mouse: A new model to study lambdoid craniosynostosis and basal cell nevus syndrome‐associated skeletal defects

“…With respect to the alteration of the skeletal elements of the cranial base, aberrant responses to both Shh and Ihh are likely involved in the defects seen in Ptch1 DL homozygous and Ptch1 DL / Ptch1 null embryos (Balczerski et al , 2012; McBratney-Owen et al , 2008; Young et al , 2006). The cranial base is derived from both mesodermal and neural crest derivatives with the basisphenoid bone acting as a boundary in association with the rostral extent of the notochord.…”

“…The cranial base is derived from both mesodermal and neural crest derivatives with the basisphenoid bone acting as a boundary in association with the rostral extent of the notochord. The notochord acts as a source of Shh and disruption of either Shh or Ihh can alter the development of the cranial base (Balczerski et al , 2012; Nagayama et al , 2008; St-Jacques et al , 1999; Young et al , 2006). Moreover, genetic manipulations that increase Hh signaling, including mice with Mks1 or Tmem107 mutations as well as a K14-Shh transgene, produce similar defects in the cranial base to the Ptch1 DL mutants (Christopher et al , 2012; Cobourne et al , 2009; Cui et al , 2011; Weatherbee et al , 2009).…”

4 Skull Base Embryology

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“…Exo-occipital somitic components contribute to the formation of the occipital bone and its elements, which is why the occipital bone represents a vertebral element that has expanded to support the brain. 6,7,[9][10][11] • During formation of the basioccipital elements, different developmental variants of the occipital condyles and craniovertebral ligaments may cause anatomic variants in the craniovertebral junction (e.g., "occipitalization" of the atlas, caused by ossification of the atlanto-occipital joint). 12 • The ossification of the occipital bone also occurs around the hypoglossal nerves, giving rise to the formation of the hypoglossal canals.…”