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[Onecut transcription factors: role in the development of the pancreas and the liver].

The development of the organism involves the formation of tissues that differ by the morphology and functions of the cells they contain. This results from the synthesis, coordinated in time and space, of a tissue-specific set of proteins. Transcription factors, which control gene expression, play a crucial role in this process. We have discovered a family of tissue-restricted transcription factors, called Onecut, whose prototype is HNF-6 (OC-1) and the two other mammalian members are OC-2 and OC-3. During embryogenesis, HNF-6 controls in the endoderm the transcription of genes which code for other transcription factors. In this way, HNF-6 regulates several developmental programs. To identify these programs, we have inactivated the Hnf6 gene in the mouse. This has shown that HNF-6 is a key factor in pancreas development and its endocrine differentiation, as well as in formation of the biliary tract. The Hnf6-/- mice develop diabetes mellitus and cholestasis. The patterns of expression of OC-2 and OC-3 superimpose partially, and coincide in part with that of HNF-6. This suggests functional interactions between the OC factors during tissue differentiation. We are tackling this question by studying the phenotype of mice in which one or several Onecut genes have been inactivated.