HNF-6 contrôle la maturation et la prolifération des hépatocytes au cours du développement embryonnaire
(2006)
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- Embryonic liver development is controlled at the transcriptional level by a network of liver-enriched transcription factors (LETFs), which regulate their mutual expression as well as that of common target genes. An important factor in this network is HNF-6. Whereas the interactions and roles of LETFs are well defined in the adult and the early embryonic liver, much less is known about their mode of action at late stages of development. The goal of the present thesis is to elucidate the role of HNF-6 in the maturation and proliferation of hepatocytes during development, and to provide a better insight into the position of HNF-6 within the LETF network. Here we show that HNF-6 plays an important and time-specific role in late embryonic liver development. On the one hand, it controls the acquisition of mature hepatocyte functions, on the other hand, it regulates epithelial and non-epithelial cell proliferation. In both cases, HNF-6 modulates the expression of genes involved in the processes. <BR> HNF-6 regulates the time-specific expression of glucose-6-phosphatase (g6pc) gene, a marker of hepatocyte maturation, via synergistic and interdependent interactions with HNF-4 and coactivator PGC-1alpha. Our study of those interactions allow us to propose a new mechanism whereby temporal specificity of gene expression requires threshold concentrations of transcription factors and their coactivators during liver development. <BR> In addition, HNF-6 controls proliferation in the liver, again in a time-specific manner, by regulating the expression of several cell cycle genes. This indirect mechanism is likely to involve HNF-6-mediated modulation of a mitogenic signal, the nature of which remains to be determined. <BR> In conclusion, our work defines a central role for HNF-6 in the hepatic network of transcription factors. Through its interactions with other factors, HNF-6 controls the timing of cell maturation and proliferation in the embryonic liver
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Beaudry, J.-B. (2006). HNF-6 contrôle la maturation et la prolifération des hépatocytes au cours du développement embryonnaire. https://hdl.handle.net/2078.5/112187