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Diverse Routes toward Early Somites in the Mouse Embryo.

Accepted version
Peer-reviewed

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Authors

Guibentif, Carolina 
Griffiths, Jonathan A 
Imaz-Rosshandler, Ivan 
Ghazanfar, Shila 

Abstract

Somite formation is foundational to creating the vertebrate segmental body plan. Here, we describe three transcriptional trajectories toward somite formation in the early mouse embryo. Precursors of the anterior-most somites ingress through the primitive streak before E7 and migrate anteriorly by E7.5, while a second wave of more posterior somites develops in the vicinity of the streak. Finally, neuromesodermal progenitors (NMPs) are set aside for subsequent trunk somitogenesis. Single-cell profiling of T-/- chimeric embryos shows that the anterior somites develop in the absence of T and suggests a cell-autonomous function of T as a gatekeeper between paraxial mesoderm production and the building of the NMP pool. Moreover, we identify putative regulators of early T-independent somites and challenge the T-Sox2 cross-antagonism model in early NMPs. Our study highlights the concept of molecular flexibility during early cell-type specification, with broad relevance for pluripotent stem cell differentiation and disease modeling.

Description

Keywords

Brachyury, cell fate regulation, developmental trajectories, neuromesodermal progenitors, somites, Animals, Body Patterning, Cell Differentiation, Cell Line, Chimera, Embryo, Mammalian, Female, Fetal Proteins, Gene Expression Profiling, Gene Expression Regulation, Developmental, Germ Cells, Heterozygote, Male, Mesoderm, Mice, Mice, Inbred C57BL, SOXB1 Transcription Factors, Single-Cell Analysis, Somites, T-Box Domain Proteins, Transcriptome

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

56

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (105031/D/14/Z)
Wellcome Trust (109081/Z/15/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
Medical Research Council (MR/M008975/1)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK106766)
Research in the authors’ laboratories is supported by the Wellcome Trust, MRC, CRUK, Blood Cancer UK, NIH-NIDDK, the Sanger-EBI Single Cell Centre; by core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust-MRC Cambridge Stem Cell Institute; and by core funding from Cancer Research UK and the European Molecular Biology Laboratory. J.A.G. was funded by Wellcome Trust award [109081/Z/15/A]. C.G. was funded by the Swedish Research Council (2017-06278). This work was funded as part of a Wellcome Strategic Award to study cell fate decisions during gastrulation (105031/D/14/Z) awarded to Wolf Reik, Berthold Göttgens, John Marioni, Jennifer Nichols, Ludovic Vallier, Shankar Srinivas, Benjamin Simons, Sarah Teichmann, and Thierry Voet.