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Foxa2 mediates critical functions of prechordal plate in patterning and morphogenesis and is cell autonomously

Zachary Harrelson1, Klaus H Kaestner, Sylvia M Evans

  • 1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , 9500 Gilman Drive MC0613C, La Jolla, CA 92093 , USA.

Biology Open
|December 6, 2012
PubMed

Insights

Foxa2 is crucial for embryonic development, particularly in the prechordal plate and ventral endoderm. Loss of Foxa2 disrupts anterior patterning, neural tube development, and foregut fusion, leading to embryonic lethality.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Axial mesendoderm, including the prechordal plate and notochord, is vital for anterior patterning.
  • Genetic tools to study these structures have been limited.
  • The winged helix transcription factor Foxa2's role in these specific lineages is not well understood.

Purpose of the Study:

  • To investigate the function of Foxa2 in the prechordal plate and ventral endoderm using Isl1-Cre driver.
  • To elucidate the role of Foxa2 in anterior neural tube and forebrain patterning.
  • To understand Foxa2's contribution to ventral foregut morphogenesis and cardiac development.

Main Methods:

  • Utilized Isl1-Cre to generate Foxa2 conditional knockout mice (Foxa2(loxP/loxP); Isl1-Cre).
  • Analyzed embryonic phenotypes at 13.5 days post-coitum (dpc).
  • Performed molecular analyses to assess gene expression in mutant embryos.

Main Results:

  • Foxa2(loxP/loxP); Isl1-Cre mutants exhibited severe defects in anterior neural tube and forebrain patterning.
  • Loss of Foxa2 in Isl1 lineages impaired expression of notochord (Brachyury) and dorsal foregut endoderm markers (Shh, Hlxb9).
  • Reduced expression of Sox17, Gata4, and ZO proteins in ventral endoderm led to failed foregut fusion and cardiac defects.

Conclusions:

  • Foxa2 is essential in the prechordal plate for notochord morphogenesis, axial patterning, and dorsal foregut endoderm development.
  • Foxa2 in ventral endoderm is required for proper foregut fusion and cardiac development by regulating Sox17, Gata4, and ZO expression.
  • Disruption of Foxa2 function in these lineages results in embryonic lethality due to multiple developmental failures.
Keywords:
Isl1axial mesendodermforegut pocketnotochord

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