期刊
DEVELOPMENT
卷 138, 期 23, 页码 5177-5188出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.067868
关键词
Apical constriction; Invagination; Rho GTPases; RhoGEF; Shroom; Mouse; Chick
资金
- National Institutes of Health [R01 EY17848, R01 CA125658]
- Abrahamson Pediatric Eye Institute Endowment at Children's Hospital Medical Center of Cincinnati
- Agence Nationale de la Recherche [ANR-07-NEURO-006-01-BRAINGEF]
- National Institute of General Medical Sciences [067525]
Epithelial invagination is a common feature of embryogenesis. An example of invagination morphogenesis occurs during development of the early eye when the lens placode forms the lens pit. This morphogenesis is accompanied by a columnar-toconical cell shape change (apical constriction or AC) and is known to be dependent on the cytoskeletal protein Shroom3. Because Shroom3-induced AC can be Rock1/2 dependent, we hypothesized that during lens invagination, RhoA, Rock and a RhoA guanine nucleotide exchange factor (RhoA-GEF) would also be required. In this study, we show that Rock activity is required for lens pit invagination and that RhoA activity is required for Shroom3-induced AC. We demonstrate that RhoA, when activated and targeted apically, is sufficient to induce AC and that RhoA plays a key role in Shroom3 apical localization. Furthermore, we identify Trio as a RhoA-GEF required for Shroom3-dependent AC in MDCK cells and in the lens pit. Collectively, these data indicate that a Trio-RhoA-Shroom3 pathway is required for AC during lens pit invagination.
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