Apical constriction and invagination downstream of the canonical Wnt signaling pathway require Rho1 and Myosin II.
Apical constriction and invagination downstream of the canonical Wnt signaling pathway require Rho1 and Myosin II.
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经典 Wnt 信号通路下游的顶端收缩和内陷需要 Rho1 和肌球蛋白 II。
DOI：
10.1016/j.ydbio.2010.01.021
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发表时间：
2010
影响因子：
2.7
通讯作者：
McCartney,BrookeM
中科院分区：
文献类型：
--
作者：
Zimmerman,SandraG;Thorpe,LaurenM;Medrano,VilmaR;Mallozzi,CarolynA;McCartney,BrookeM
肿瘤抑制基因腺瘤性息肉病大肠杆菌 (APC) 是细胞骨架组织中 Wnt 信号传导和功能的负调节因子。结肠上皮细胞中人类 APC 的破坏会引发良性息肉，并在额外突变后进展为癌症。人们对息肉病的早期事件知之甚少，对于经典 Wnt 信号在正常上皮结构和形态发生中的作用也是如此。为了确定模型上皮细胞中 APC 完全丧失的后果，我们在果蝇翼成虫盘中生成了 APC2 APC1 双无效克隆。 APC 丢失会导致分离、顶端收缩和内陷，这是由经典 Wnt 信号传导的转录激活引起的。此外，我们表明细胞命运的 Wnt 依赖性变化可以与细胞形状的 Wnt 依赖性变化脱钩。据报道，Wnt 激活会上调翼盘中的 DE-钙粘蛋白，并且 DE-钙粘蛋白升高被认为会促进顶端收缩。我们发现 APC 无效组织的顶端收缩和内陷与 DE-钙粘蛋白升高无关，但依赖于肌球蛋白 II 活性。此外，我们发现 Rho1 的破坏会抑制 APC 无效细胞的顶端收缩和内陷。我们的数据表明经典 Wnt 信号传导与上皮结构之间存在新的联系，需要激活 Rho1 途径和肌球蛋白 II。
The tumor suppressor Adenomatous polyposis coli (APC) is a negative regulator of Wnt signaling and functions in cytoskeletal organization. Disruption of human APC in colonic epithelia initiates benign polyps that progress to carcinoma following additional mutations. The early events of polyposis are poorly understood, as is the role of canonical Wnt signaling in normal epithelial architecture and morphogenesis. To determine the consequences of complete loss of APC in a model epithelium, we generated APC2 APC1 double null clones in the Drosophila wing imaginal disc. APC loss leads to segregation, apical constriction, and invagination that result from transcriptional activation of canonical Wnt signaling. Further, we show that Wnt-dependent changes in cell fate can be decoupled from Wnt-dependent changes in cell shape. Wnt activation is reported to upregulate DE-cadherin in wing discs, and elevated DE-cadherin is thought to promote apical constriction. We find that apical constriction and invagination of APC null tissue are independent of DE-cadherin elevation, but are dependent on Myosin II activity. Further, we show that disruption of Rho1 suppresses apical constriction and invagination in APC null cells. Our data suggest a novel link between canonical Wnt signaling and epithelial structure that requires activation of the Rho1 pathway and Myosin II.