Open AccessRho kinase-dependent apical constriction counteracts M-phase apical expansion to enable mouse neural tube closure
Author(s) -
Max B. Butler,
Nina E. Short,
Eirini Maniou,
Paula Alexandre,
Nicholas D. E. Greene,
Andrew J. Copp,
Gabriel L. Galea
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.230300
Subject(s) - apical constriction , neuroepithelial cell , biology , microbiology and biotechnology , neural tube , cell cycle , apical cell , anatomy , biophysics , cell , embryo , morphogenesis , biochemistry , neural stem cell , stem cell , gene
Cellular generation of mechanical forces required to close the presumptive spinal neural tube, the ‘posterior neuropore’ (PNP), involves interkinetic nuclear migration (INM) and apical constriction. Both processes change the apical surface area of neuroepithelial cells, but how they are biomechanically integrated is unknown. Rho kinase (Rock; herein referring to both ROCK1 and ROCK2) inhibition in mouse whole embryo culture progressively widens the PNP. PNP widening is not caused by increased mechanical tension opposing closure, as evidenced by diminished recoil following laser ablation. Rather, Rock inhibition diminishes neuroepithelial apical constriction, producing increased apical areas in neuroepithelial cells despite diminished tension. Neuroepithelial apices are also dynamically related to INM progression, with the smallest dimensions achieved in cells positive for the pan-M phase marker Rb phosphorylated at S780 (pRB-S780). A brief (2 h) Rock inhibition selectively increases the apical area of pRB-S780-positive cells, but not pre-anaphase cells positive for phosphorylated histone 3 (pHH3 + ). Longer inhibition (8 h, more than one cell cycle) increases apical areas in pHH3 + cells, suggesting cell cycle-dependent accumulation of cells with larger apical surfaces during PNP widening. Consequently, arresting cell cycle progression with hydroxyurea prevents PNP widening following Rock inhibition. Thus, Rock-dependent apical constriction compensates for the PNP-widening effects of INM to enable progression of closure. This article has an associated First Person interview with the first authors of the paper .