RT Journal Article
T1 Integrin-Mediated Focal Anchorage Drives Epithelial Zippering during Mouse Neural Tube Closure.
A1 Molè, Matteo A
A1 Galea, Gabriel L
A1 Rolo, Ana
A1 Weberling, Antonia
A1 Nychyk, Oleksandr
A1 De Castro, Sandra C
A1 Savery, Dawn
A1 Fässler, Reinhard
A1 Ybot-González, Patricia
A1 Greene, Nicholas D E
A1 Copp, Andrew J
K1 cell adhesion
K1 epithelial zippering
K1 extracellular matrix
K1 fibronectin
K1 fusion
K1 gap closure
K1 integrins
K1 morphogenesis
K1 neurulation
K1 spina bifida
AB Epithelial fusion is a key process of morphogenesis by which tissue connectivity is established between adjacent epithelial sheets. A striking and poorly understood feature of this process is "zippering," whereby a fusion point moves directionally along an organ rudiment. Here, we uncover the molecular mechanism underlying zippering during mouse spinal neural tube closure. Fusion is initiated via local activation of integrin β1 and focal anchorage of surface ectoderm cells to a shared point of fibronectin-rich basement membrane, where the neural folds first contact each other. Surface ectoderm cells undergo proximal junction shortening, establishing a transitory semi-rosette-like structure at the zippering point that promotes juxtaposition of cells across the midline enabling fusion propagation. Tissue-specific ablation of integrin β1 abolishes the semi-rosette formation, preventing zippering and causing spina bifida. We propose integrin-mediated anchorage as an evolutionarily conserved mechanism of general relevance for zippering closure of epithelial gaps whose disturbance can produce clinically important birth defects.
YR 2020
FD 2020
LK http://hdl.handle.net/10668/15090
UL http://hdl.handle.net/10668/15090
LA en
DS RISalud
RD Apr 7, 2025