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Actomyosin contractility and a threshold of cadherin cell adhesion are required during tissue fusion.

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Τίτλος: Actomyosin contractility and a threshold of cadherin cell adhesion are required during tissue fusion.
Συγγραφείς: Teng CS; Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA.; Program in Craniofacial Biology, University of California San Francisco , San Francisco, CA, USA.; Institute for Human Genetics, University of California San Francisco , San Francisco, CA, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco , San Francisco, CA, USA., Curtis SW; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA., Brewer GC; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA., Leslie-Clarkson EJ; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA., Bush JO; Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA.; Program in Craniofacial Biology, University of California San Francisco , San Francisco, CA, USA.; Institute for Human Genetics, University of California San Francisco , San Francisco, CA, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco , San Francisco, CA, USA.
Πηγή: The Journal of cell biology [J Cell Biol] 2026 Jan 05; Vol. 225 (1). Date of Electronic Publication: 2025 Nov 13.
Τύπος έκδοσης: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 0375356 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-8140 (Electronic) Linking ISSN: 00219525 NLM ISO Abbreviation: J Cell Biol Subsets: MEDLINE
Imprint Name(s): Original Publication: New York : Rockefeller University Press
Ιατρικοί όροι (MeSH): Cadherins*/metabolism , Cadherins*/genetics , Actomyosin*/metabolism , Actomyosin*/genetics , Cleft Lip*/genetics , Cleft Lip*/metabolism , Cleft Lip*/pathology , Cell Adhesion*, Catenins/metabolism ; Catenins/genetics ; Actins/metabolism ; rhoA GTP-Binding Protein/metabolism ; rhoA GTP-Binding Protein/genetics ; Animals ; Humans ; Mice ; Delta Catenin ; Morphogenesis
Περίληψη: Tissue fusion is integral to mammalian morphogenesis, and its failure is a significant cause of structural anomalies, yet the underlying cellular mechanisms are incompletely understood. We examine cellular drivers of upper lip fusion in the mammalian embryo by establishing a live-imaging modality, revealing specific enrichment of F-actin that propagates in multicellular cables anchored at the fusion site. Actomyosin contractility drives lip fusion, and its pharmacological or genetic attenuation results in failed fusion and cleft lip. Generating a series of mice deficient in specific p120-catenin molecular functions, we reveal that p120-catenin binding to RhoA and Kaiso is dispensable during mammalian development, while stabilization of cadherins is crucial. Through generating an allelic series of new compound P-cadherin/E-cadherin mouse mutations disrupting combined cadherin levels, we unveil an elevated cadherin cell adhesion threshold requirement specific to upper lip fusion. Finally, we identify CDH3 variants in individuals with cleft lip, supporting the relevance of this mechanism in human tissue fusion.
(© 2025 Teng et al.)
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Grant Information: K01DE033989 United States NH NIH HHS; K01 DE033989 United States DE NIDCR NIH HHS; R35DE031926 United States NH NIH HHS; F32 DE030367 United States DE NIDCR NIH HHS; F32DE030367 United States NH NIH HHS; R35 DE031926 United States DE NIDCR NIH HHS
Substance Nomenclature: 0 (Cadherins)
9013-26-7 (Actomyosin)
0 (Catenins)
0 (Delta Catenin)
0 (Actins)
EC 3.6.5.2 (rhoA GTP-Binding Protein)
0 (Ctnnd1 protein, mouse)
Entry Date(s): Date Created: 20251113 Date Completed: 20251113 Latest Revision: 20260623
Update Code: 20260624
PubMed Central ID: PMC12614168
DOI: 10.1083/jcb.202503070
PMID: 41231213
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1540-8140
DOI:10.1083/jcb.202503070