Neural stem cell transcriptional networks highlight genes essential for nervous system development.
Neural stem cells must strike a balance between self-renewal and multipotency, and differentiation. Identification of the transcriptional networks regulating stem cell division is an essential step in understanding how this balance is achieved. We have shown that the homeodomain transcription factor, Prospero, acts to repress self-renewal and promote differentiation. Among its targets are three neural stem cell transcription factors, Asense, Deadpan and Snail, of which Asense and Deadpan are repressed by Prospero. Here, we identify the targets of these three factors throughout the genome. We find a large overlap in their target genes, and indeed with the targets of Prospero, with 245 genomic loci bound by all factors. Many of the genes have been implicated in vertebrate stem cell self-renewal, suggesting that this core set of genes is crucial in the switch between self-renewal and differentiation. We also show that multiply bound loci are enriched for genes previously linked to nervous system phenotypes, thereby providing a shortcut to identifying genes important for nervous system development.
Southall
Tony D
TD
The Gurdon Institute and The Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Brand
Andrea H
AH
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001665:Binding Sites; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C407353:ase protein, Drosophila; C073099:pros protein, Drosophila; C000604451:sna protein, Drosophila; C078020:Dpn protein, Drosophila