Regulation of Sox2 by STAT3 initiates commitment to the neural precursor cell fate.
STAT3, a member of the signal transducer and activator or transcription (STAT) family of proteins, plays a major role in gliogenesis; however, its functions during differentiation of neural precursor cells (NPCs) are unclear. Our data demonstrate that STAT3 is present and active in the developing mouse central nervous system (CNS) as early as E7.5, several days prior to gliogenesis. We hypothesize that STAT3 is functioning very early in neural development to regulate NPC differentiation. To test this hypothesis, STAT3 dominant negative embryonic stem (ES) cells were generated and subjected to neural differentiation. The loss of STAT3 resulted in production of significantly fewer NPCs along with decreased expression of the neural stem cell marker nestin. Further investigation revealed the existence of a novel signaling pathway during early neural development in which STAT3 directly regulates the Sox2 promoter leading to Sox2 expression and subsequent nestin expression and commitment to the NPC fate.
Foshay
Kara M
KM
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Gallicano
G Ian
GI
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins / Q000235:genetics* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D054258:Neural Plate / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic; D055748:SOXB1 Transcription Factors; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D055748:SOXB1 Transcription Factors; D050796:STAT3 Transcription Factor; C527783:Sox2 protein, mouse; C494087:Stat3 protein, mouse; D014157:Transcription Factors