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June 18, 1999Science725 citations

Initiation of Mammalian Liver Development from Endoderm by Fibroblast Growth Factors

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JJJoonil JungMZMing‐Hua ZhengMGMitchell Goldfarb

Key Points

  • Identify the signaling factors secreted by cardiac mesoderm that instruct mammalian foregut endoderm to initiate liver development.
  • Treated isolated foregut endoderm from mouse embryos with recombinant FGF1, FGF2, or FGF8 in culture absent cardiac mesoderm.
  • Assessed hepatic gene induction and tissue morphogenesis alongside expression profiles of FGF receptors 1 and 4 using growth factors and specific inhibitors.
  • FGF1 and FGF2, but not FGF8, substituted for cardiac mesoderm to activate the hepatic gene expression program in endoderm coexpressing FGF receptors 1 and 4.
  • FGF8 signaling facilitated the morphogenetic outgrowth of the hepatic endoderm following initial liver gene induction.

Abstract

The signaling molecules that elicit embryonic induction of the liver from the mammalian gut endoderm or induction of other gut-derived organs are unknown. Close proximity of cardiac mesoderm, which expresses fibroblast growth factors (FGFs) 1, 2, and 8, causes the foregut endoderm to develop into the liver. Treatment of isolated foregut endoderm from mouse embryos with FGF1 or FGF2, but not FGF8, was sufficient to replace cardiac mesoderm as an inducer of the liver gene expression program, the latter being the first step of hepatogenesis. The hepatogenic response was restricted to endoderm tissue, which selectively coexpresses FGF receptors 1 and 4. Further studies with FGFs and their specific inhibitors showed that FGF8 contributes to the morphogenetic outgrowth of the hepatic endoderm. Thus, different FGF signals appear to initiate distinct phases of liver development during mammalian organogenesis.

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Cite This Study

Jung et al. (1999) studied this question.

synapsesocial.com/papers/69daa4212d871caad68359a2https://doi.org/10.1126/science.284.5422.1998
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