Abstracts
Résumé
Le gène hairless (hr) des mammifères code pour une protéine nucléaire impliquée dans le contrôle du renouvellement du follicule pileux. Cette protéine est un cofacteur de récepteurs nucléaires d’hormones qui régulent la transcription de gènes cibles au cours de la différentiation de l’épiderme et du cycle du poil. La protéine Hairless (HR) fait partie de grands complexes multiprotéiques capables de réprimer la transcription, en association avec des facteurs de remodelage de la chromatine comme les histones désacétylases. Chez les mammifères, le locus hairless est la cible de nombreuses mutations alléliques dont les effets sont pléiotropiques. Ces altérations entraînent l’apparition d’un phénotype cutané complexe, caractérisé par la perte progressive et irréversible d’un pelage d’apparence normale au cours des premières semaines de vie post-natale. L’analyse de la littérature sur le gène hairless chez la souris et chez l’homme permet d’attribuer des différences morphologiques spécifiques à chaque mutant, aussi bien au niveau de l’épiderme et du follicule pileux que dans d’autres tissus où le gène est exprimé au cours du développement. Ces résultats suggèrent que l’intégrité du gène hairless est requise pour le déroulement correct de la morphogenèse d’organes aussi différents que l’épiderme, l’oreille interne, l’ovaire ou le thymus. Le gène hairless semble ainsi faire partie de circuits et de cascades d’interactions géniques dont le contrôle moléculaire est fondamentalement inconnu. La variété des phénotypes alléliques souligne l’importance de l’analyse moléculaire du locus hairless pour identifier les altérations géniques impliquées dans les différentes mutations détectées. Les recherches concernant la mutation hairless ont été particulièrement dynamiques pendant les dernières années, depuis que l’homologue de ce gène a pu être mis en évidence chez l’homme. Cependant, un bon nombre de questions reste en suspens, notamment quant au site exact d’activité du gène hairless au sein des nombreuses populations cellulaires du follicule pileux, son rôle précis au cours de la morphogenèse, sa localisation au sein des voies de signalisation, ainsi que l’identité des partenaires et des cibles de la protéine Hairless.
Summary
The hairless gene in mammals encodes a nuclear factor that is highly expressed in skin and appears to control hair follicle integrity and cycling. In the absence of a normal and functional Hairless (Hr) protein, the hair bulb undergoes premature apoptosis during the first catagen stage of the hair cycle. The most striking effects of the mutation are loss of hair follicles and formation of epidermal utricles and dermal cysts. The hairless gene expression appears to be widespread and temporally regulated. The gene is strongly expressed in different compartments of the brain. Hairless mRNAs were detected in cartilage, gonads, thymus and colon. In addition to alopecia, hairless mice strains show subtle defects in the development and differentiation of various tissues and organs. The Hr protein is localised in cell nuclei and functions as a transcriptional regulator. Although its role has not been resolved in molecular terms, it was demonstrated that Hr is able to interact with multiple nuclear hormone receptors. Hr seems to be a part of a large multiprotein complex capable to repress transcription by its association to chromatin remodelling factors such as histone deacetylases. Recent experimental data suggest that Hr might be involved in Hox gene regulation, cell adhesion modulation and progenitor cells identity. At least in the skin, but probably in other organs, the Hr repressor seems to be responsible for the timing of epithelial cells differentiation.
Appendices
Références
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