Co-expression of Tbx6 and Sox2 identifies a novel transient neuromesoderm progenitor cell state

Development. 2017 Dec 15;144(24):4522-4529. doi: 10.1242/dev.153262. Epub 2017 Oct 30.

Abstract

Elongation of the body axis is a key aspect of body plan development. Bipotential neuromesoderm progenitors (NMPs) ensure axial growth of embryos by contributing both to the spinal cord and mesoderm. The current model for the mechanism controlling NMP deployment invokes Tbx6, a T-box factor, to drive mesoderm differentiation of NMPs. Here, we identify a new population of Tbx6+ cells in a subdomain of the NMP niche in mouse embryos. Based on co-expression of a progenitor marker, Sox2, we identify this population as representing a transient cell state in the mesoderm-fated NMP lineage. Genetic lineage tracing confirms the presence of the Tbx6+ NMP cell state. Furthermore, we report a novel aspect of the documented Tbx6 mutant phenotype, namely an increase from two to four ectopic neural tubes, corresponding to the switch in NMP niche, thus highlighting the importance of Tbx6 function in NMP fate decision. This study emphasizes the function of Tbx6 as a bistable switch that turns mesoderm fate 'on' and progenitor state 'off', and thus has implications for the molecular mechanism driving NMP fate choice.

Keywords: Axial elongation; Mouse; Neuromesoderm progenitors; Tbx6; Trunk-tail transition.

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Body Patterning / physiology
  • Cell Differentiation
  • Cell Lineage
  • Embryonic Stem Cells / cytology*
  • Gene Expression Regulation, Developmental
  • Mesoderm / cytology*
  • Mice
  • Mice, Transgenic
  • Neural Tube / cytology
  • Neural Tube / embryology*
  • SOXB1 Transcription Factors / biosynthesis*
  • SOXB1 Transcription Factors / genetics
  • Spinal Cord / embryology*
  • T-Box Domain Proteins
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • T-Box Domain Proteins
  • Tbx6 protein, mouse
  • Transcription Factors