SOX9 induces and maintains neural stem cells.
Neural stem cells (NSCs) are uncommitted cells of the CNS defined by their multipotentiality and ability to self renew. We found these cells to not be present in substantial numbers in the CNS until after embryonic day (E) 10.5 in mouse and E5 in chick. This coincides with the induction of SOX9 in neural cells. Gain- and loss-of-function studies indicated that SOX9 was essential for multipotent NSC formation. Moreover, Sonic Hedgehog was able to stimulate precocious generation of NSCs by inducing Sox9 expression. SOX9 was also necessary for the maintenance of multipotent NSCs, as shown by in vivo fate mapping experiments in the adult subependymal zone and olfactory bulbs. In addition, loss of SOX9 led 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.
Scott
Charlotte E
CE
Division of Stem Cell Biology and Developmental Genetics, Medical Research Council, National Institute for Medical Research (NIMR), Mill Hill, London, UK.
Wynn
Sarah L
SL
Sesay
Abdul
A
Cruz
Catarina
C
Cheung
Martin
M
Gomez Gaviro
Maria-Victoria
MV
Booth
Sarah
S
Gao
Bo
B
Cheah
Kathryn S E
KS
Lovell-Badge
Robin
R
Briscoe
James
J
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002645:Chickens; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D055758:SOX9 Transcription Factor; D055748:SOXB1 Transcription Factors; D012794:Sialic Acids; C527783:Sox2 protein, mouse; C527933:Sox9 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; C485184:enhanced green fluorescent protein; C103469:polysialyl neural cell adhesion molecule; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine