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

• Published in: Developmental biology Vol. 371; no. 2; pp. 203 - 214
• Main Authors: Balczerski, B., Zakaria, S., Tucker, A.S., Borycki, A.G., Koyama, E., Pacifici, M., Francis-West, P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-11-2012
• Subjects: Animals; Axial skeleton; Bone and Bones - embryology; Bone and Bones - metabolism; bone morphogenetic proteins; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; bones; brain; cell viability; Chick Embryo; Chickens; chicks; Chondrogenesis; Cranial base; Cranial mesoderm; Craniofacial skeleton; Embryo, Mammalian - metabolism; Gene Expression Regulation, Developmental; head; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; Mesoderm - metabolism; Mice; Signal Transduction; skeleton; Skull - embryology; Skull - metabolism; Sonic hedgehog; Craniofacial skeleton; Sonic hedgehog; Cranial base; Chondrogenesis; Cranial mesoderm; Axial skeleton
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2012.08.011

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.
► Development of the cranial base is distinct from the trunk skeleton. ► Hh signalling is required for development of the cranial base and cell survival. ► There is a delay in cranial base development relative to the axial skeleton. ► The early cranial mesoderm is refractory to Hh signalling.