Saxena Aditya, Denholm Barry, Bunt Stephanie, Bischoff Marcus, VijayRaghavan Krishnaswamy, Skaer Helen
Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
Department of Zoology, University of Cambridge, Cambridge, United Kingdom; School of Biology, St Andrews, Scotland, United Kingdom.
PLoS Biol. 2014 Dec 2;12(12):e1002013. doi: 10.1371/journal.pbio.1002013. eCollection 2014 Dec.
Most epithelial tubes arise as small buds and elongate by regulated morphogenetic processes including oriented cell division, cell rearrangements, and changes in cell shape. Through live analysis of Drosophila renal tubule morphogenesis we show that tissue elongation results from polarised cell intercalations around the tubule circumference, producing convergent-extension tissue movements. Using genetic techniques, we demonstrate that the vector of cell movement is regulated by localised epidermal growth factor (EGF) signalling from the distally placed tip cell lineage, which sets up a distal-to-proximal gradient of pathway activation to planar polarise cells, without the involvement for PCP gene activity. Time-lapse imaging at subcellular resolution shows that the acquisition of planar polarity leads to asymmetric pulsatile Myosin II accumulation in the basal, proximal cortex of tubule cells, resulting in repeated, transient shortening of their circumferential length. This repeated bias in the polarity of cell contraction allows cells to move relative to each other, leading to a reduction in cell number around the lumen and an increase in tubule length. Physiological analysis demonstrates that animals whose tubules fail to elongate exhibit abnormal excretory function, defective osmoregulation, and lethality.
大多数上皮管起源于小芽,并通过包括定向细胞分裂、细胞重排和细胞形状变化在内的调控形态发生过程而伸长。通过对果蝇肾小管形态发生的实时分析,我们发现组织伸长是由围绕肾小管周长的极化细胞插入导致的,产生了汇聚延伸组织运动。利用基因技术,我们证明细胞运动的方向是由远端尖端细胞谱系的局部表皮生长因子(EGF)信号调控的,该信号建立了从远端到近端的信号通路激活梯度,从而使细胞平面极化,而无需PCP基因活性的参与。亚细胞分辨率的延时成像显示,平面极性的获得导致肌球蛋白II在肾小管细胞基底近端皮质中不对称的脉动积累,导致其圆周长度反复短暂缩短。细胞收缩极性的这种反复偏向使得细胞能够相对移动,导致管腔周围细胞数量减少,肾小管长度增加。生理学分析表明,肾小管未能伸长的动物表现出异常的排泄功能、渗透调节缺陷和致死性。