αE-catenin-dependent mechanotransduction is essential for proper convergent extension in zebrafish.
Cadherin complexes mediate cell-cell adhesion and are crucial for embryonic development. Besides their structural function, cadherin complexes also transduce tension across the junction-actomyosin axis into proportional biochemical responses. Central to this mechanotransduction is the stretching of the cadherin-F-actin-linker α-catenin, which opens its central domain for binding to effectors such as vinculin. Mechanical unfolding of α-catenin leads to force-dependent reinforcement of cadherin-based junctions as studied in cell culture. The importance of cadherin mechanotransduction for embryonic development has not been studied yet. Here we used TALEN-mediated gene disruption to perturb endogenous αE-catenin in zebrafish development. Zygotic α-catenin mutants fail to maintain their epithelial barrier, resulting in tissue rupturing. We then specifically disrupted mechanotransduction, while maintaining cadherin adhesion, by expressing an αE-catenin construct in which the mechanosensitive domain was perturbed. Expression of either wild-type or mechano-defective α-catenin fully rescues barrier function in α-catenin mutants; however, expression of mechano-defective α-catenin also induces convergence and extension defects. Specifically, the polarization of cadherin-dependent, lamellipodia-driven cell migration of the lateral mesoderm was lost. These results indicate that cadherin mechanotransduction is crucial for proper zebrafish morphogenesis, and uncover one of the essential processes affected by its perturbation.
Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht 3584CG, The Netherlands.
Mitchell K L
MK
Han
The Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center Utrecht, Uppsalalaan 8, Utrecht 3584CT, The Netherlands.
Esteban
E
Hoijman
The Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center Utrecht, Uppsalalaan 8, Utrecht 3584CT, The Netherlands.
Emily
E
Nöel
The Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center Utrecht, Uppsalalaan 8, Utrecht 3584CT, The Netherlands.
Laurence
L
Garric
The Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center Utrecht, Uppsalalaan 8, Utrecht 3584CT, The Netherlands Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, Utrecht 3584 CM, The Netherlands.
Jeroen
J
Bakkers
Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht 3584CG, The Netherlands j.derooij-3@umcutrecht.nl.
Johan
http://orcid.org/0000-0001-6101-7875
J
de Rooij
Alpha-catenin; Cadherin mechanotransduction; Convergent extension; Embryogenesis; Zebrafish