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Rôle des répresseurs transcriptionnels Hes1/4 dans la maintenance des cellules souches rétiniennes chez Xenopus laevis

Abstract : The retina of fish and amphibian contains genuine neural stem cells located at the most peripheral edge of the ciliary marginal zone (CMZ). However, their cell-of-origin as well as the mechanisms that sustain their maintenance during development are presently unknown. We identified Hes1 and Hes4 (previously named XHairy1 and XHairy2, respectively), genes encoding bHLHO transcriptional repressors, as stem cell specific markers of the CMZ that are positively regulated by the canonical Wnt pathway and differentially regulated by Hedgehog signalling. We found that during retinogenesis, Hes1/4 labels a small territory, located first at the pigmented epithelium (RPE)/neural retina (NR) border and latter in the retinal margin, that likely gives rise to adult retinal stem cells. Our gain of function experiments show that Hes1/4 cell autonomously prevent retinal precursor cells from commitment towards retinal fates and maintain them in a proliferative state. Besides, our data highlight for the first time that Hes1/4 may also constitute crucial regulators of cell cycle kinetics. Hes1/4 gain of function indeed significantly slow down cell division, mainly through the lengthening of G1 phase. As a whole, we propose that Hes1/4 maintain particular stemness features in a cellular cohort dedicated to constitute the adult retinal stem cell pool, by keeping it in an undifferentiated and slowly proliferative state along embryonic retinogenesis.
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Submitted on : Thursday, October 18, 2012 - 9:47:22 AM
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Warif Abdelhamid El Yakoubi. Rôle des répresseurs transcriptionnels Hes1/4 dans la maintenance des cellules souches rétiniennes chez Xenopus laevis. Biologie du développement. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA11T052⟩. ⟨tel-00743085⟩

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