Initiation of Mammalian Liver Development from Endoderm by Fibroblast Growth Factors

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.

Sustained Delivery Growth Factors with Polyethyleneimine‐Modified Nanoparticles Promote Embryonic Stem Cells Differentiation and Liver Regeneration

“…Activin A has been reported to induce definitive endoderm differentiation of ESCs;10, 32 DE cells constitute the embryonic germ layer that produces hepatic cells;33 aFGF and HGF are essential for liver development, with aFGF efficiently initiating hepatic differentiation of ESCs from the definitive endoderm and HGF promoting hepatic growth 34, 35. The novel growth factors delivery system was prepared by mixing Activin A, aFGF, and HGF with positively charged PEI‐MSNs.…”

Pancreas organogenesis: From bud to plexus to gland

“…It has been well studied in chick (Le Douarin, 1963) and mouse (Gualdi et al, 1996) that an endodermal interaction with cardiac mesoderm is required for proper hepatic differentiation. FGF signaling can induce hepatic differentiation in endodermal explants in the absence of cardiac mesoderm, while the prevention of FGF signaling from cardiac mesoderm makes ventral foregut endoderm unable to assume a hepatic fate (Jung et al 1999). Instead, pancreas fate is initiated, and has raised the perhaps debatable conclusion that the ''default fate'' of ventral foregut endoderm is pancreas (Deutsch et al, 2001).…”

“…Recent studies, however, more strongly link the origin of the extrahepatobiliary primordium to the tissue that forms the ventral pancreas, rather than the liver. Sox17, a major regulator of endoderm formation (Kanai-Azuma et al, 2002), is required to establish and maintain distinct boundaries between the liver, EHB, and ventral pancreas domains. Loss of Sox17 function after gastrulation leads to biliary agenesis and ectopic pancreas formation, whereas Sox17 misexpression suppresses pancreas development by promoting ectopic biliary-like tissue within the posterior foregut region that expresses the posterior foregut and pancreas marker gene Pdx1.…”

Pluripotent plasticity of stem cells and liver repopulation

“…66,68 Oxidative stress is thought to play a major role in the pathogenesis of both alcoholic and NAFLD. 69,70 The replicative activity of mature hepatocytes is also known to be inhibited in patients with alcoholic hepatitis, 71 rodents with alcohol-induced fatty livers 72 and in some animal models of NAFLD. 73,74 Although the combination of oxidative liver damage and inhibited hepatocyte proliferation provides a strong stimulus for oval cell accumulation in the liver, whether or not this cell population is expanded in FLD has never been studied.…”