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  Antagonistic Activities of Sox2 and Brachyury Control the Fate Choice of Neuro-Mesodermal Progenitors

Koch, F., Scholze, M., Wittler, L., Schifferl, D., Sudheer, S., Grote, P., et al. (2017). Antagonistic Activities of Sox2 and Brachyury Control the Fate Choice of Neuro-Mesodermal Progenitors. Developmental Cell, 42, 514-526. doi:10.1016/j.devcel.2017.07.021.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-D637-F Version Permalink: http://hdl.handle.net/21.11116/0000-0000-C796-6
Genre: Journal Article

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 Creators:
Koch, Frederic1, Author              
Scholze, Manuela1, Author              
Wittler, Lars1, Author              
Schifferl, Dennis1, Author              
Sudheer, Smita1, Author              
Grote, Phillip1, Author              
Timmermann, Bernd2, Author              
Macura, Karol1, Author              
Herrmann, Bernhard G.1, Author              
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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Free keywords: NMP; chromatin; lineage choice; mesoderm; mouse; neuro-mesodermal progenitors; neuroectoderm; single-cell analysis; transcriptome; trunk development
 Abstract: The spinal cord and mesodermal tissues of the trunk such as the vertebral column and skeletal musculature derive from neuro-mesodermal progenitors (NMPs). Sox2, Brachyury (T), and Tbx6 have been correlated with NMP potency and lineage choice; however, their exact role and interaction in these processes have not yet been revealed. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from embryonic day 8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch toward the mesodermal fate. Sox2 acts antagonistically and promotes neural development. T is also involved in remodeling the chromatin for mesodermal development. Tbx6 reinforces the mesodermal fate choice, represses the progenitor state, and confers paraxial fate commitment. Our findings refine previous models and establish molecular principles underlying mammalian trunk development, comprising NMP maintenance, lineage choice, and mesoderm formation.

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Language(s): eng - English
 Dates: 2017-08-172017-09-11
 Publication Status: Published in print
 Pages: 13
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.devcel.2017.07.021
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Title: Developmental Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 42 Sequence Number: - Start / End Page: 514 - 526 Identifier: ISSN: 1534-5807
CoNE: /journals/resource/111006902714134