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Blastomere Explants to Test for Cell Fate Commitment During Embryonic Development
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FOXF1 inhibits hematopoietic lineage commitment during early mesoderm specification.

Maud Fleury1, Alexia Eliades1, Peter Carlsson2

  • 1Cancer Research UK Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.

Development (Cambridge, England)
|August 22, 2015
PubMed
Summary

The transcription factor FOXF1 regulates mesoderm development. FOXF1 expression restrains hematopoietic cell specification, distinguishing it from other mesodermal lineages during gastrulation.

Keywords:
GastrulationHemangioblastMesoderm

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Genetics

Background:

  • Early mesoderm specification and cell fate decisions are critical for embryonic development but remain poorly understood.
  • The role of specific transcription factors in regulating these early lineage choices is a key area of investigation.

Purpose of the Study:

  • To investigate the role of the Forkhead transcription factor FOXF1 in mesoderm specification.
  • To determine how FOXF1 influences cell fate decisions in nascent mesodermal precursors both in vitro and in vivo.

Main Methods:

  • Investigated FOXF1 expression and function in differentiating mouse embryonic stem cells (in vitro).
  • Analyzed FOXF1's role in vivo during gastrulation in mouse embryos.
  • Utilized lineage tracing and gene expression analysis to identify FOXF1-expressing cell populations and their derivatives.

Main Results:

  • FOXF1 marks specific mesodermal lineages, including smooth muscle and endothelial cells in vitro, and extra-embryonic mesoderm derivatives (chorion, allantois, amnion) in vivo.
  • FOXF1 expression is excluded from hematopoietic cells and blood islands both in vitro and in vivo.
  • Foxf1 deficiency leads to increased primitive erythropoiesis, while enforced FOXF1 expression represses hematopoiesis, indicating an inverse correlation.

Conclusions:

  • FOXF1 is a key regulator of mesoderm specification during gastrulation, marking extra-embryonic mesoderm but excluding the blood lineage.
  • FOXF1 actively restrains the specification of mesodermal progenitors towards hematopoiesis, highlighting its role in lineage restriction.