The canonical Wnt pathway directly regulates NRSF/REST expression in chick spinal cord.
Neural precursor cells actively proliferate in the ventricular zone to self-renew the stem cell population, and in parallel, maintain their undifferentiated state. This progenitor pool generates postmitotic cells that migrate to the mantle layer and differentiate into mature neurons. The growth of these stem cells is strictly controlled by the canonical Wnt signaling cascade, in part mediated by the direct regulation of Cyclin D1, a critical regulator of cell cycle progression. Here, we report that the canonical Wnt pathway directly controls the expression of NRSF/REST. The Wnt-activated beta-catenin/TCF complex up-regulates this gene through a conserved element found in its exon 1a, a critical result obtained by a novel in ovo transcriptional assay. Hence, our data show that the canonical Wnt signaling cascade directly regulates the NRSF/REST and Cyclin D1 genes, thereby controlling the progenitor cells. In addition, we show that our in ovo transcription assay is a powerful way to analyze gene regulation in a natural in vivo context.
Institute of Development, Aging and Cancer, Tohoku University, Aoba, Sendai, Miyagi, Japan.
Shigeki
S
Nishihara
Leo
L
Tsuda
Toshihiko
T
Ogura
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D019938:Cyclin D1; D029721:Drosophila Proteins / Q000378:metabolism*; D018274:Electroporation / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099229:RE1-Silencing Transcription Factor
D019938:Cyclin D1; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099229:RE1-Silencing Transcription Factor; C120397:RSF1 protein, Drosophila