Diverse Routes toward Early Somites in the Mouse Embryo

Carolina Guibentif,Carolina Guibentif,Carolina Guibentif,Carolina Guibentif,Jonathan A Griffiths,John C Marioni,John C Marioni,John C Marioni,John C Marioni,Berthold Göttgens,Berthold Göttgens,Berthold Göttgens,Shila Ghazanfar,Shila Ghazanfar,Valerie Wilson,Valerie Wilson,Jennifer Nichols,Jennifer Nichols,Jennifer Nichols,Ivan Imaz-Rosshandler

doi:10.1016/j.devcel.2020.11.013

Abstract

SummarySomite 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.

Highlights

The recent emergence of high throughput single-cell RNAsequencing assays has allowed researchers to survey entire transcriptional landscapes of development in numerous species (Cao et al, 2019; Packer et al, 2019; Pijuan-Sala et al, 2019; Wagner et al, 2018)
We investigated the transcriptional similarity between these populations and other cell types related to axial elongation at E8.5—neuromesodermal progenitors (NMPs) and spinal cord
Homeobox transcription factor expression supported an underlying spatial component to this ordering, with caudal Cdx genes peaking in the center, at the position of NMPs (Figures 1E and S1G)

Summary

Introduction

The recent emergence of high throughput single-cell RNAsequencing (scRNA-seq) assays has allowed researchers to survey entire transcriptional landscapes of development in numerous species (Cao et al, 2019; Packer et al, 2019; Pijuan-Sala et al, 2019; Wagner et al, 2018). Somites are transient segments of the paraxial mesoderm that give rise to the axial skeleton and associated musculature. Following formation of the most anterior somites, subsequent axis elongation is fueled by a pool of neuromesodermal progenitors (NMPs), which give rise to neural components of the spinal cord as well as the mesodermal tissue of the somites (Pourquie , 2001; Tzouanacou et al, 2009). NMPs are characterized by co-expression of transcription factors associated with gastrulation, mesodermal, and neural development, including Brachyury (T), Sox, and Nkx (Henrique et al, 2015; Steventon and Martinez Arias, 2017; Wilson et al, 2009). Gene-expression analysis has demonstrated a specific molecular make-up of the anterior-most somites

Methods

Results

Discussion

Conclusion