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

Kwanha Yu, Sean McGlynn, Michael P. Matise

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Cell 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 (ShhFP) 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 ShhFP 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 ShhFP in regulating the specification and differentiation of glial and epithelial cells in the mouse spinal cord.

Original languageEnglish (US)
Pages (from-to)1594-1604
Number of pages11
JournalDevelopment (Cambridge)
Volume140
Issue number7
DOIs
StatePublished - Apr 1 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Keywords

  • Astrocytes
  • Ependymal zone
  • Hedgehog
  • Mouse
  • Oligodendrocytes
  • Signaling center
  • Stem cells

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