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Related Experiment Videos

Repressive and restrictive mesodermal interactions with gut endoderm: possible relation to Meckel's Diverticulum.

P Bossard1, K S Zaret

  • 1Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Development (Cambridge, England)
|October 25, 2000
PubMed
Summary

Mouse embryo gut development involves two inhibitory signals from mesoderm. These signals progressively restrict endoderm potential, guiding intestinal cell differentiation and preventing liver gene activation. This process is crucial for normal gut formation.

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Area of Science:

  • Developmental biology
  • Molecular biology
  • Genetics

Background:

  • The mouse embryo's midgut and hindgut endoderm form the intestinal epithelium.
  • The mechanisms determining intestinal cell fate versus other endoderm-derived cell types remain unclear.
  • Previous studies showed intestinal endoderm's pluripotence, activating liver genes when isolated from mesoderm.

Purpose of the Study:

  • To elucidate the signaling interactions between mesoderm and endoderm that govern intestinal differentiation.
  • To identify the timing and nature of mesodermal inhibitory activities on endoderm development.
  • To investigate the role of transcription factors HNF3 (Foxa2) and GATA in this process.

Main Methods:

  • Tissue explant studies on mouse embryos at different gestational ages (8.5-13.5 days).

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  • Analysis of gene expression patterns, specifically liver-specific genes and transcription factors (HNF3/Foxa2, GATA).
  • Chromatin binding assays to assess transcription factor activity.

    • Main Results:

    • At 13.5 days gestation, mouse embryonic mesoderm acquires a second inhibitory activity.
    • This activity irreversibly represses HNF3 (Foxa2) and GATA factor expression in the endoderm.
    • This repression precedes intestinal cytodifferentiation and restricts endoderm's potential to activate liver genes.

    Conclusions:

    • Two sequential inhibitory interactions from the mesoderm progressively restrict the developmental potential of the gut endoderm.
    • These interactions are essential for directing endoderm towards intestinal differentiation.
    • The study also identified potential murine models of Meckel's Diverticulum, suggesting a link between absent mesodermal interactions and congenital abnormalities.