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

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...

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Bibliographic Details
Published in:	eLife Vol. 10
Main Authors:	Romanos, Michèle, Allio, Guillaume, Roussigné, Myriam, Combres, Léa, Escalas, Nathalie, Soula, Cathy, Médevielle, François, Steventon, Benjamin, Trescases, Ariane, Bénazéraf, Bertrand
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 05-10-2021 eLife Sciences Publications Ltd eLife Sciences Publication eLife Sciences Publications, Ltd
Subjects:	Animals bird embryos Birds Cell Differentiation - genetics Cell Differentiation - physiology Cell Lineage cell motility Developmental Biology DNA binding proteins Embryo, Nonmammalian - physiology Embryonic development Embryos Experiments Fetal Proteins - genetics Gene Expression Gene Expression Regulation, Developmental heterogeneity Life Sciences mathematical modeling Mathematical models Mathematics Mesoderm Morphogenesis Motility Neural stem cells Neural tube neuromesodermal progenitors Progenitor cells Proteins Quail SOXB1 Transcription Factors - genetics Stem cells T-Box Domain Proteins - genetics Transcription factors cell motility morphogenesis neuromesodermal progenitors developmental biology mathematical modeling bird embryos heterogeneity
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.66588