Inversin relays Frizzled-8 signals to promote proximal pronephros development
Inversin relays Frizzled-8 signals to promote proximal pronephros development
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DOI：
10.1073/pnas.1013070107
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发表时间：
2010-11-23
影响因子：
11.1
通讯作者：
Walz, Gerd
中科院分区：
文献类型：
--
作者：
Lienkamp, Soeren;Ganner, Athina;Walz, Gerd
倒位素突变导致II型肾单位营养不良，这是一种以囊性肾病和发育缺陷为特征的婴儿常染色体隐性遗传疾病。反转蛋白调节Wnt信号传导，并且在早期胚胎发生期间是会聚延伸运动所需的。我们现在表明，反转蛋白是必不可少的爪蟾前肾形成，涉及两种不同的和相反的形式的细胞运动。敲除反转蛋白废除近端原肾延伸和远端小管分化，表型类似的非洲爪蟾缺乏卷曲-8。外源性Inversin修复了由缺乏Frizzled-8引起的前肾缺陷，表明Inversin在前肾形态发生中作用于Frizzled-8的下游。反转蛋白的消耗防止响应于卷曲蛋白-8的Dishevelled的募集，并阻止Dishevelled在体内肾小管上皮细胞的顶膜处的积累。因此，肾小管形态发生缺陷似乎与II型肾单位结核患者中观察到的肾脏病理学有关。
Mutations of inversin cause type II nephronophthisis, an infantile autosomal recessive disease characterized by cystic kidney disease and developmental defects. Inversin regulates Wnt signaling and is required for convergent extension movements during early embryogenesis. We now show that Inversin is essential for Xenopus pronephros formation, involving two distinct and opposing forms of cell movements. Knockdown of Inversin abrogated both proximal pronephros extension and distal tubule differentiation, phenotypes similar to that of Xenopus deficient in Frizzled-8. Exogenous Inversin rescued the pronephric defects caused by lack of Frizzled-8, indicating that Inversin acts downstream of Frizzled-8 in pronephros morphogenesis. Depletion of Inversin prevents the recruitment of Dishevelled in response to Frizzled-8 and impeded the accumulation of Dishevelled at the apical membrane of tubular epithelial cells in vivo. Thus, defective tubule morphogenesis seems to contribute to the renal pathology observed in patients with nephronophthisis type II.