Shi Dongbo, Komatsu Kouji, Hirao Mayumi, Toyooka Yayoi, Koyama Hiroshi, Tissir Fadel, Goffinet André M, Uemura Tadashi, Fujimori Toshihiko
Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
Development. 2014 Dec;141(23):4558-68. doi: 10.1242/dev.115659. Epub 2014 Nov 18.
The oviduct is an important organ in reproduction where fertilization occurs, and through which the fertilized eggs are carried to the uterus in mammals. This organ is highly polarized, where the epithelium forms longitudinal folds along the ovary-uterus axis, and the epithelial multicilia beat towards the uterus to transport the ovulated ova. Here, we analyzed the postnatal development of mouse oviduct and report that multilevel polarities of the oviduct are regulated by a planar cell polarity (PCP) gene, Celsr1. In the epithelium, Celsr1 is concentrated in the specific cellular boundaries perpendicular to the ovary-uterus axis from postnatal day 2. We found a new feature of cellular polarity in the oviduct - the apical surface of epithelial cells is elongated along the ovary-uterus axis. In Celsr1-deficient mice, the ciliary motion is not orchestrated along the ovary-uterus axis and the transport ability of beating cilia is impaired. Epithelial cells show less elongation and randomized orientation, and epithelial folds show randomized directionality and ectopic branches in the mutant. Our mosaic analysis suggests that the geometry of epithelial cells is primarily regulated by Celsr1 and as a consequence the epithelial folds are aligned. Taken together, we reveal the characteristics of the multilevel polarity formation processes in the mouse oviduct epithelium and suggest a novel function of the PCP pathway for proper tissue morphogenesis.
输卵管是生殖过程中的一个重要器官，受精在此发生，并且在哺乳动物中，受精卵通过它被输送到子宫。这个器官高度极化，其上皮沿着卵巢 - 子宫轴形成纵向褶皱，上皮多纤毛朝着子宫跳动以运输排卵后的卵子。在这里，我们分析了小鼠输卵管的出生后发育，并报告输卵管的多级极性受平面细胞极性（PCP）基因Celsr1调控。在出生后第2天起，上皮中的Celsr1集中在垂直于卵巢 - 子宫轴的特定细胞边界处。我们发现了输卵管细胞极性的一个新特征——上皮细胞的顶端表面沿着卵巢 - 子宫轴伸长。在Celsr1基因缺失的小鼠中，纤毛运动没有沿着卵巢 - 子宫轴协调，且摆动纤毛的运输能力受损。上皮细胞伸长减少且方向随机，突变体中的上皮褶皱方向随机且出现异位分支。我们的镶嵌分析表明上皮细胞的形态主要由Celsr1调控，因此上皮褶皱得以排列整齐。综上所述，我们揭示了小鼠输卵管上皮多级极性形成过程的特征，并提出了PCP信号通路在适当组织形态发生中的新功能。
