Apical constriction and invagination downstream of the canonical Wnt signaling pathway require Rho1 and Myosin II

Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Developmental Biology (Impact Factor: 3.55). 04/2010; 340(1):54-66. DOI: 10.1016/j.ydbio.2010.01.021
Source: PubMed


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.

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    • "We thus explored the reason for this apparent discrepancy. As noted above, in addition to affecting Arm levels and activating Wnt target genes, activating Wnt signaling in clones of cells in imaginal discs has drastic consequences for cell morphology—cells with activated Wnt signaling apically constrict, distorting the epithelial sheet [27], [28]. This can be clearly seen in some clonal patches, where co-staining with actin reveals groups of mutant cells with strongly constricted apical ends (Fig. 4A, yellow arrowhead in boxed region, yellow arrowhead in inset). "
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