Étude génétique du développement normal et pathologique des canaux de Müller

Abstract : Female genital tract onset and differentiation is a complex developmental process. Molecular and cellular mechanisms involved in this process are triggered by numerous genes and signaling pathways in between which multiple interactions take place. In a clinical point of view, accurate knowledge of these interactions is of great importance, for the understanding of pathogenic mechanisms causing congenital anomalies of the reproductive system in women. Complementarily, genetic studies of malformation syndromes affecting the female inner genital tract, contribute to better define the molecular cascade eliciting the development of this essential organ. In this context two research programs, one fundamental and another clinical, have been developed. In the first one, the role of mTcf7l2 gene was investigated during inner male and female genital tract development in the mouse. This gene encodes a nuclear component of the Wnt pathways and is subject to many alternative splicing events. Its expression pattern was established during the müllerian ducts (the anlagen of inner female genital tract) differentiation. The overall results suggest that mTcf7l2 takes part in the sexually dimorphic development of the inner genital tract. The second part of the program consisted in a genetic study of a cohort of patients presenting with diagnosed MRKH syndrome. This study has led us to define four microdeletions located within four discrete critical regions linked the DiGeorge syndrome, a disease of which the malformation spectrum overlaps with that of MRKH syndrome. This has raised the question whether MRKH and DiGeorge syndromes correspond to various manifestations of a unique and heterogeneous deletion syndrome or are parts of a wider contiguous gene syndrome, according to the affected chromosome. Accurate delineation of one of these deletions has led to define ITIH5 as a candidate gene. Preliminary expression studies in the mouse suggest that this gene would play a major role during müllerian ducts differentiation.
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Submitted on : Monday, February 1, 2010 - 10:35:58 AM
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  • HAL Id : tel-00451925, version 1

Citation

Tanguy Watrin. Étude génétique du développement normal et pathologique des canaux de Müller. Sciences du Vivant [q-bio]. Université Rennes 1, 2009. Français. ⟨tel-00451925⟩

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