Murine Hepatoblasts

ABSTRACT: The homeobox transcription factor Prox1 is expressed in embryonic hepatoblasts and remains expressed in adult hepatocytes. Prox1-null mice show severe deficiencies of liver development, but the underlying mechanisms are unknown. We studied the effects of Prox1 on the transcriptional profile of embryonic day-14 (ED14) met-murine-hepatocytes (ED14-MMH). These immortalized murine hepatoblasts express numerous hepatoblast markers, but not Prox1. We performed stable transfection with Prox1 cDNA, analyzed the transcriptome with Agilent mouse whole genome microarrays and validated genes by qRT-PCR. We observed more than 12-fold up-regulation of 22 genes and down-regulation of 232 genes. Numerous of these genes are involved in metabolic hepatocyte functions and may be regulated by Prox1 directly or indirectly, e.g. by down-regulation of HNF4a. Prox1 induces down-regulation of transcription factors, which are highly expressed in neighboring endodermal organs, suggesting a function during hepatoblast commitment. Prox1 does not influence proliferative activity of MMH but regulates genes involved in liver morphogenesis. We observed up-regulation of both type-IVa3 procollagen and functionally active matrix metalloproteinase-2 (MMP-2), which places Prox1 in the centre of liver matrix turnover. This is consistent with MMP-2 expression in hepatoblasts during liver development, and persistence of a basal lamina around the liver bud in Prox1-deficient mice. Our studies suggest that Prox1 is a multifunctional regulator of liver morphogenesis, hepatocyte function and commitment. Keywords: Met murine hepatocytes - Hex - HNF4a - MMP-2 - Type-IV collagen Keywords: Met murine hepatocytes - Hex - HNF4a - MMP-2 - Type-IV collagen

ORGANISM(S): Mus musculus

PROVIDER: GSE7867 | GEO | 2007/05/25

SECONDARY ACCESSION(S): PRJNA100007

REPOSITORIES: GEO