hgf/c-met expression and functional analysis during zebrafish embryogenesis

Abstract

Hepatocyte growth factor (HGF) and its receptor tyrosine kinase Met are linked to several processes underlying vertebrate development and cancer progression. Here, we characterized the expression of zebrafish c-met, hgf1, and hgf2 from cleavage stages through organogenesis and initiated an analysis of Met signaling. We identified c-met as a marker of endoderm and demonstrated that its expression can be activated downstream of Nodal. Injection of c-met mRNA drives expression of the endodermal gene sox17. During gastrulation, hgf1 transcripts are visible in mesendodermal cells along the midline. Later, c-met is expressed in kidney, islet2-positive neurons, and liver. We show that hgf1 is transcribed during gastrulation while hgf1 and hgf2 are detectable in pharyngeal arches and swim bladder. Similar to mouse, knockdown of zebrafish Met reduces liver size. Our results suggest a role for Met during endoderm specification and indicate that mechanisms of liver development are conserved between mammals and bony fish. © 2008 Wiley-Liss, Inc.