Dermal Skeleton: Morphogenesis

 


Because the notochord, a powerful inductive agent, only reaches up to the cranial flexure, it encourages a cartilage template only at the base of the skull. Above the notochord, a mesoderm-originated covering lies over the developing brain, preventing cartilage from forming [B]. This membrane ultimately gives rise to the roof and side bones of the skull as well as the dermis covering them. The plate-like bones are separated during development by connective tissue sutures [A]. Premature fusion of these sutures results in craniosynostosis, which causes an abnormally shaped skull and associated neural problems. This condition helps to explain the signaling mechanisms between the forming dermal bone and the underlying neural tissue.

The dura mater is the hardest of three layers encasing the brain, and lies closest to the ossifying mesenchyme. In the embryonic stage, the dura mater and the mesenchyme express a lot of Msx-1, Msx2, as well as Bmp-4 and FGF-9. This signaling keeps the sutures between the plates open, allowing the skull bones to grow and accommodate the expanding brain. After birth, sonic hedgehog is expressed at the edges of the skull bones, causing the dura mater to stop expressing signaling factors. This signaling dictates the mophogenesis of the bones.
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Malformations of the brain are accompanied by malformations of the skull. When the brain is very small, microcephaly occurs: the skull forms a very small vault. In the opposite situation, where the brain is swollen with excess cerebrospinal fluid, the skull is greatly enlarged in a situation called hydrocephaly[A]. The signifigance of this communication is that the communication between neural and mesenchymal tissue causes the skull to form a custom made case for the brain during its rapid proliferation in the embryonic stage.

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