SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells.
The mechanisms that establish and maintain the multipotency of stem cells are poorly understood. In neural crest stem cells (NCSCs), the HMG-box factor SOX10 preserves not only glial, but surprisingly, also neuronal potential from extinction by lineage commitment signals. The latter function is reflected in the requirement of SOX10 in vivo for induction of MASH1 and PHOX2B, two neurogenic transcription factors. Simultaneously, SOX10 inhibits or delays overt neuronal differentiation, both in vitro and in vivo. However, this activity requires a higher Sox10 gene dosage than does the maintenance of neurogenic potential. The opponent functions of SOX10 to maintain neural lineage potentials, while simultaneously serving to inhibit or delay neuronal differentiation, suggest that it functions in stem or progenitor cell maintenance, in addition to its established role in peripheral gliogenesis.
Kim
Jaesang
J
Howard Hughes Medical Institute, Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125, USA.
Lo
Liching
L
Dormand
Emma
E
Anderson
David J
DJ
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000502:physiology; D009419:Nerve Tissue Proteins; D009432:Neural Crest / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D051381:Rats; D055757:SOXE Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C100935:Phox2a protein, rat; D055757:SOXE Transcription Factors; C527925:Sox10 protein, rat; D014157:Transcription Factors; D016212:Transforming Growth Factor beta