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Neural progenitors adopt specific identities by directly repressing all alternative progenitor transcriptional programs

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Item Type:Article
Title:Neural progenitors adopt specific identities by directly repressing all alternative progenitor transcriptional programs
Creators Name:Kutejova, E. and Sasai, N. and Shah, A. and Gouti, M. and Briscoe, J.
Abstract:In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues.
Keywords:Basic Helix-Loop-Helix Transcription Factors, Body Patterning, Cell Differentiation, Cell Line, Cell Lineage, Chick Embryo, Developmental Gene Expression Regulation, Genetic Transcription, Homeodomain Proteins, Nerve Tissue Proteins, Neural Stem Cells, Signal Transduction, Transcription Factors, Animals, Mice
Source:Developmental Cell
ISSN:1534-5807
Publisher:Cell Press / Elsevier
Volume:36
Number:6
Page Range:639-653
Date:21 March 2016
Official Publication:https://doi.org/10.1016/j.devcel.2016.02.013
PubMed:View item in PubMed

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