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  Reconstruction of the Gene Regulatory Network Involved in the Sonic Hedgehog Pathway with a Potential Role in Early Development of the Mouse Brain

Liu, J., Wang, X., Li, J., Wang, H., Wei, G., & Yan, J. (2014). Reconstruction of the Gene Regulatory Network Involved in the Sonic Hedgehog Pathway with a Potential Role in Early Development of the Mouse Brain. PLoS Computational Biology, 10(10): e1003884.

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Liu, Jinhua1, Author              
Wang, Xuelong, Author
Li, Juan, Author
Wang, Haifang, Author
Wei, Gang, Author
Yan, Jun, Author
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1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

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 Abstract: The Sonic hedgehog (Shh) signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1− and Shh−Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh−Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1− domain and down-regulates the genes characteristic of the Shh−Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

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Language(s): eng - English
 Dates: 2014-10-09
 Publication Status: Published online
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 Rev. Type: Peer
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Title: PLoS Computational Biology
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 10 (10) Sequence Number: e1003884 Start / End Page: - Identifier: ISSN: 1553-734X
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000017180_1