A Trio-RhoA-Shroom3 pathway is required for apical constriction and epithelial invagination.
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-to-conical 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.
The Visual Systems Group, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Timothy F
TF
Plageman
Bharesh K
BK
Chauhan
Christine
C
Yang
Fanny
F
Jaudon
Xun
X
Shang
Yi
Y
Zheng
Ming
M
Lou
Anne
A
Debant
Jeffrey D
JD
Hildebrand
Richard A
RA
Lang
D000818:Animals; D002460:Cell Line; D048430:Cell Shape / Q000502:physiology*; D002642:Chick Embryo; D016616:Cryoultramicrotomy; D004285:Dogs; D018274:Electroporation; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D007908:Lens, Crystalline / Q000196:embryology*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012044:Regression Analysis; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; D010750:Phosphoproteins; C402112:Shrm protein, mouse; C490975:Trio protein, mouse; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein