SOX9, acting downstream of Sonic hedgehog signalling, induces and maintains neural stem cells

Charlotte Elizabeth Scott (1) , Sarah L. Wynn (1) , Abdul K. Sesay (1) , Catarina Cruz (1) , Martin Cheung (1) , Maria Victoria Gomez-Gaviro (1) , Sarah Booth (1) , Bo Gao (1) , Kathryn Se Cheah (1) , Robin Lovell-Badge (1) , James Briscoe (1)

1 Division of Stem Cell Biology and Developmental Genetics

Neural stem cells (NSCs) are uncommitted cells of the central nervous system (CNS) defined by their multipotentiality and ability to self renew. We found that these cells are not present in substantial numbers in the CNS until after E10.5 in mouse and E5 in chick. This coincides with the induction of SOX9 in neural cells. Gain and loss-of-function studies indicate that SOX9 is essential for multipotent NSC formation. Moreover, Sonic Hedgehog is able to stimulate precocious generation of NSCs by inducing Sox9 expression. SOX9 is also necessary for the maintenance of multipotent NSCs, as shown by in vivo fate mapping experiments in the adult subependymal zone (SEZ) and olfactory bulbs. In addition, loss of SOX9 leads ependymal cells to adopt a neuroblast identity. These data identify a functional link between extrinsic and intrinsic mechanisms of NSCs specification and maintenance, and establish a central role for SOX9 in the process.

Mots clés: Development; Glia; Proliferation; Differentiation

Charlotte Elizabeth Scott, Sarah L. Wynn, Abdul K. Sesay, Catarina Cruz, Martin Cheung, et al.. SOX9, acting downstream of Sonic hedgehog signalling, induces and maintains neural stem cells. Nature Neuroscience, 2010, 13 (10), pp.1181. ⟨10.1038/nn.2646⟩. ⟨hal-00580084⟩