Dynamic origins of a self-pulled epithelial zipper We are using ascidian embryos as a simple model to understand the dynamics of neural tube closure. During the last step of neural tube closure, known as zippering, the neural folds meet and fuse from posterior to anterior, replacing heterotypic contacts between neural and epidermal cells with homotypic (neural/neural or epidermal/epidermal) contacts. We have found that zippering is driven by two overlapping spatiotemporal patterns of RhoA and Myosin II activity: A posterior-to-anterior wave of activity drives the sequential shortening of heterotypic cell contacts along the neural folds just ahead of the advancing zipper. A tissue level asymmetry in RhoA/Myosin II, plus dissipation of tissue-level resistance behind the zipper converts these local junction contractions into unidirectional zipper movement. Both of these patterns are controlled by tissue-specific expression of a classical cadherin Cad-2 in neural cells. Cad-2 promotes activation of RhoA and Myosin II at heterotypic contacts ahead of the zipper and inhibition at homotypic contacts behind the zipper to create the tissue level asymmetry. Cad-2 also promotes downregulation of adhesion on heterotypic contacts, actuating a tissue-level feedback loop in which: (a) local zipper advance concentrates forces that act perpendicular to heterotypic contacts to (b) promote local contact separation, which (c) induces local activation of RhoA/Myosin along separated contacts to drive further zipper advance. Together, these activities induce a self- propagating wave of morphogenetic activity to drive zippering and neural tube closure.

Team webpage: MUNRO LAB

Friday, September 13, 2024, 11 a.m.
Biochemistry Center Conference Room