Abstract
SummaryEpithelial 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.
Highlights
Epithelial fusion is a process of tissue morphogenesis through which pairs of epithelial sheets become apposed and eventually united at their edges to form a continuous layer
Epithelial fusion is a key process of morphogenesis by which tissue connectivity is established between adjacent epithelial sheets
Fusion is initiated via local activation of integrin b1 and focal anchorage of surface ectoderm cells to a shared point of fibronectin-rich basement membrane, where the neural folds first contact each other
Summary
Epithelial fusion is a process of tissue morphogenesis through which pairs of epithelial sheets become apposed and eventually united at their edges to form a continuous layer. The process of epithelial fusion can be first observed during morphogenesis of the vertebrate NT, where fine coordination between elevation and fusion progression transforms the flat neural plate into a closed tube. This establishes epithelial continuity of the surface ectoderm (SE) and neuroepithelium (NE) between apposing neural folds along the entire rostro-caudal axis of the developing embryo. Primary neurulation is completed once the caudal-most region of the open NT, known as the posterior neuropore (PNP), becomes sealed Failure to complete this last phase of spinal closure results in open spina bifida (Copp et al, 2015), a defect that arises during the first month of human embryonic development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
