Cell non-autonomy amplifies disruption of neurulation by mosaic Vangl2 deletion in mice.

Autor: Galea GL; Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK. g.galea@ucl.ac.uk.; Comparative Bioveterinary Sciences, Royal Veterinary College, London, UK. g.galea@ucl.ac.uk., Maniou E; Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK., Edwards TJ; Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK., Marshall AR; Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK., Ampartzidis I; Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK., Greene NDE; Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK., Copp AJ; Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Feb 19; Vol. 12 (1), pp. 1159. Date of Electronic Publication: 2021 Feb 19.
DOI: 10.1038/s41467-021-21372-4
Abstrakt: Post-zygotic mutations that generate tissue mosaicism are increasingly associated with severe congenital defects, including those arising from failed neural tube closure. Here we report that neural fold elevation during mouse spinal neurulation is vulnerable to deletion of the VANGL planar cell polarity protein 2 (Vangl2) gene in as few as 16% of neuroepithelial cells. Vangl2-deleted cells are typically dispersed throughout the neuroepithelium, and each non-autonomously prevents apical constriction by an average of five Vangl2-replete neighbours. This inhibition of apical constriction involves diminished myosin-II localisation on neighbour cell borders and shortening of basally-extending microtubule tails, which are known to facilitate apical constriction. Vangl2-deleted neuroepithelial cells themselves continue to apically constrict and preferentially recruit myosin-II to their apical cell cortex rather than to apical cap localisations. Such non-autonomous effects can explain how post-zygotic mutations affecting a minority of cells can cause catastrophic failure of morphogenesis leading to clinically important birth defects.
Databáze: MEDLINE
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