Dintilhac Agnès, Bihan Réjane, Guerrier Daniel, Deschamps Stéphane, Bougerie Héloise, Watrin Tanguy, Bonnec Georgette, Pellerin Isabelle
UMR 6061, Genetique et Developpement, IFR 140, Universite de Rennes 1, Campus Villejean, Rennes, France.
Int J Dev Biol. 2005;49(7):851-8. doi: 10.1387/ijdb.052013ad.
While studies have highlighted the role of HOXA9-13 and PBX1 homeobox genes during the development of the female genital tract, the molecular mechanisms triggered by these genes are incompletely elucidated. In several developmental pathways, PBX1 binds to MEINOX family members in the cytoplasm to be imported into the nucleus where they associate with HOX proteins to form a higher complex that modulates gene expression. This concept has been challenged by a recent report showing that in some cell cultures, PBX1 nuclear localization might be regulated independently of MEINOX proteins (Kilstrup-Nielsen et al., 2003). Our work gives the first illustration of this alternative mechanism in an organogenesis process. Indeed, we show that PBX1 is mostly cytoplasmic in epithelial endometrial cells of the developing female genital tract despite the nuclear localization of MEIS1. We thus provide evidence for a control of PBX1 intracellular distribution which is independent of MEINOX proteins, but is cell cycle correlated.
虽然研究强调了HOXA9 - 13和PBX1同源框基因在女性生殖道发育过程中的作用,但由这些基因触发的分子机制尚未完全阐明。在几种发育途径中,PBX1在细胞质中与MEINOX家族成员结合,然后被导入细胞核,在那里它们与HOX蛋白结合形成一个更高层次的复合物来调节基因表达。最近的一份报告对这一概念提出了挑战,该报告表明,在一些细胞培养中,PBX1的核定位可能独立于MEINOX蛋白进行调节(Kilstrup - Nielsen等人,2003年)。我们的工作首次展示了这种替代机制在器官发生过程中的情况。事实上,我们发现尽管MEIS1定位于细胞核,但在发育中的女性生殖道的子宫内膜上皮细胞中,PBX1大多位于细胞质中。因此,我们提供了证据,证明PBX1的细胞内分布是独立于MEINOX蛋白进行控制的,但与细胞周期相关。