PMID- 28826820 OWN - NLM STAT- MEDLINE DCOM- 20170925 LR - 20181202 IS - 1878-1551 (Electronic) IS - 1534-5807 (Linking) VI - 42 IP - 5 DP - 2017 Sep 11 TI - Antagonistic Activities of Sox2 and Brachyury Control the Fate Choice of Neuro-Mesodermal Progenitors. PG - 514-526.e7 LID - S1534-5807(17)30597-X [pii] LID - 10.1016/j.devcel.2017.07.021 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Koch, Frederic AU - Koch F AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Scholze, Manuela AU - Scholze M AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Wittler, Lars AU - Wittler L AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Schifferl, Dennis AU - Schifferl D AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Sudheer, Smita AU - Sudheer S AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Grote, Phillip AU - Grote P AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Timmermann, Bernd AU - Timmermann B AD - Sequencing Core Facility, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Macura, Karol AU - Macura K AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany. FAU - Herrmann, Bernhard G AU - Herrmann BG AD - Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany; Institute for Medical Genetics, Charite - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Electronic address: herrmann@molgen.mpg.de. LA - eng PT - Journal Article DEP - 20170817 PL - United States TA - Dev Cell JT - Developmental cell JID - 101120028 RN - 0 (Chromatin) RN - 0 (Fetal Proteins) RN - 0 (SOXB1 Transcription Factors) RN - 0 (T-Box Domain Proteins) RN - 0 (Tbx6 protein, mouse) RN - 0 (Transcription Factors) RN - EQ43SC3GDB (Brachyury protein) SB - IM MH - Animals MH - Base Sequence MH - Cell Lineage/*genetics MH - Chromatin/metabolism MH - Chromatin Assembly and Disassembly/genetics MH - Fetal Proteins/genetics/*metabolism MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental MH - Mesoderm/*cytology MH - Mice MH - Models, Biological MH - Neurons/*cytology/metabolism MH - SOXB1 Transcription Factors/genetics/*metabolism MH - Single-Cell Analysis MH - Stem Cells/*cytology/metabolism MH - T-Box Domain Proteins/genetics/*metabolism MH - Transcription Factors/metabolism MH - Wnt Signaling Pathway/genetics OTO - NOTNLM OT - NMP OT - chromatin OT - lineage choice OT - mesoderm OT - mouse OT - neuro-mesodermal progenitors OT - neuroectoderm OT - single-cell analysis OT - transcriptome OT - trunk development EDAT- 2017/08/23 06:00 MHDA- 2017/09/26 06:00 CRDT- 2017/08/23 06:00 PHST- 2017/01/26 00:00 [received] PHST- 2017/06/07 00:00 [revised] PHST- 2017/07/24 00:00 [accepted] PHST- 2017/08/23 06:00 [pubmed] PHST- 2017/09/26 06:00 [medline] PHST- 2017/08/23 06:00 [entrez] AID - S1534-5807(17)30597-X [pii] AID - 10.1016/j.devcel.2017.07.021 [doi] PST - ppublish SO - Dev Cell. 2017 Sep 11;42(5):514-526.e7. doi: 10.1016/j.devcel.2017.07.021. Epub 2017 Aug 17.