Cell-to-cell heterogeneity in Sox2 and Bra expression guides progenitor motility and destiny

Elife. 2021 Oct 5:10:e66588. doi: 10.7554/eLife.66588.

Abstract

Although cell-to-cell heterogeneity in gene and protein expression within cell populations has been widely documented, we know little about its biological functions. By studying progenitors of the posterior region of bird embryos, we found that expression levels of transcription factors Sox2 and Bra, respectively involved in neural tube (NT) and mesoderm specification, display a high degree of cell-to-cell heterogeneity. By combining forced expression and downregulation approaches with time-lapse imaging, we demonstrate that Sox2-to-Bra ratio guides progenitor's motility and their ability to stay in or exit the progenitor zone to integrate neural or mesodermal tissues. Indeed, high Bra levels confer high motility that pushes cells to join the paraxial mesoderm, while high levels of Sox2 tend to inhibit cell movement forcing cells to integrate the NT. Mathematical modeling captures the importance of cell motility regulation in this process and further suggests that randomness in Sox2/Bra cell-to-cell distribution favors cell rearrangements and tissue shape conservation.

Keywords: bird embryos; cell motility; developmental biology; heterogeneity; mathematical modeling; morphogenesis; neuromesodermal progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Differentiation / physiology
  • Cell Lineage
  • Embryo, Nonmammalian / physiology*
  • Fetal Proteins / genetics*
  • Gene Expression Regulation, Developmental*
  • Gene Expression*
  • Quail
  • SOXB1 Transcription Factors / genetics*
  • T-Box Domain Proteins / genetics*

Substances

  • Fetal Proteins
  • SOXB1 Transcription Factors
  • T-Box Domain Proteins
  • Brachyury protein

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.