Floor plate-derived sonic hedgehog regulates glial and ependymal cell fates in the developing spinal cord

Abstract

SUMMARYCell fate specification in the CNS is controlled by the secreted morphogen sonic hedgehog (Shh). At spinal cord levels, Shh produced by both the notochord and floor plate (FP) diffuses dorsally to organize patterned gene expression in dividing neural and glial progenitors. Despite the fact that two discrete sources of Shh are involved in this process, the individual contribution of the FP, the only intrinsic source of Shh throughout both neurogenesis and gliogenesis, has not been clearly defined. Here, we have used conditional mutagenesis approaches in mice to selectively inactivate Shh in the FP (Shh FP ) while allowing expression to persist in the notochord, which underlies the neural tube during neurogenesis but not gliogenesis. We also inactivated Smo, the common Hh receptor, in neural tube progenitors. Our findings confirm and extend prior studies suggesting an important requirement for Shh FP in specifying oligodendrocyte cell fates via repression of Gli3 in progenitors. Our studies also uncover a connection between embryonic Shh signaling and astrocyte-mediated reactive gliosis in adults, raising the possibility that this pathway is involved in the development of the most common cell type in the CNS. Finally, we find that intrinsic spinal cord Shh signaling is required for the proper formation of the ependymal zone, the epithelial cell lining of the central canal that is also an adult stem cell niche. Together, our studies identify a crucial late embryonic role for Shh FP in regulating the specification and differentiation of glial and epithelial cells in the mouse spinal cord.

Developmental Pattern Formation in Phases

“…This is consistent with previous experimental observations [8][9][10][11] and indicates that the specification of pattern and neuronal differentiation are separate phases of spinal cord development ( Figure 1A). Following the neurogenic phase, the progenitors are not depleted, but transition to generate distinct glial cell types [12,13].…”

The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord

“…Ependymal cells lining the central canal of the spinal cord are derived from ventral neuroepithelial progenitors (Fu et al, 2003;Yu et al, 2013). The ependyma is composed of a layer of ciliated mural ependymocytes interspersed with tanycytes and CSF-contacting neurons (Bruni, 1998;Meletis et al, 2008;Sabourin et al, 2009;Marichal et al, 2012).…”

Dynamics of Sonic hedgehog signaling in the ventral spinal cord are controlled by intrinsic changes in source cells requiring Sulfatase 1

“…However, our results reveal that MFP induction and formation of the p3 domain in zebrafish follow different schedules than in amniotes. In chicken and mouse, the ventral patterning is indeed initially influenced by an Shh gradient emanating from the notochord, and shh expression in the prospective MFP is induced secondarily to nkx2.2 upregulation (Chamberlain et al, 2008;Jeong and McMahon, 2005;Lek et al, 2010;Matise et al, 1998;Ribes et al, 2010;Yu et al, 2013). In zebrafish, shh expression in MFP cells precedes nkx2.2a expression.…”