title: Cellular basis of neuroepithelial bending during mouse spinal neural tube closure.
abstract: Bending of the neural plate at paired dorsolateral hinge points (DLHPs) is required for neural tube closure in the spinal region of the mouse embryo. As a step towards understanding the morphogenetic mechanism of DLHP development, we examined variations in neural plate cellular architecture and proliferation during closure. Neuroepithelial cells within the median hinge point (MHP) contain nuclei that are mainly basally located and undergo relatively slow proliferation, with a 7 h cell cycle length. In contrast, cells in the dorsolateral neuroepithelium, including the DLHP, exhibit nuclei distributed throughout the apico-basal axis and undergo rapid proliferation, with a 4 h cell cycle length. As the neural folds elevate, cell numbers increase to a greater extent in the dorsolateral neural plate that contacts the surface ectoderm, compared with the more ventromedial neural plate where cells contact paraxial mesoderm and notochord. This marked increase in dorsolateral cell number cannot be accounted for solely on the basis of enhanced cell proliferation in this region. We hypothesised that neuroepithelial cells may translocate in a ventral-to-dorsal direction as DLHP formation occurs, and this was confirmed by vital cell labelling in cultured embryos. The translocation of cells into the neural fold, together with its more rapid cell proliferation, leads to an increase in cell density dorsolaterally compared with the more ventromedial neural plate. These findings suggest a model in which DLHP formation may proceed through 'buckling' of the neuroepithelium at a dorso-ventral boundary marked by a change in cell-packing density.
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Suzanne G
authors.initials: SG
authors.lastname: McShane
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Matteo A
authors.initials: MA
authors.lastname: Molè
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Dawn
authors.initials: D
authors.lastname: Savery
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Nicholas D E
authors.initials: ND
authors.lastname: Greene
authors.affiliation: Embryology Unit, Children's Medical Research Institute and Sydney Medical School, University of Sydney, Westmead, New South Wales 2145, Australia.
authors.forename: Patrick P L
authors.initials: PP
authors.lastname: Tam
authors.affiliation: Newlife Birth Defects Research Centre, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. Electronic address: a.copp@ucl.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copp
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004622:Embryo, Mammalian; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009432:Neural Crest / Q000166:cytology; D054258:Neural Plate / Q000166:cytology / Q000196:embryology*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology*; D046569:Neuroepithelial Cells / Q000166:cytology*; D054261:Neurulation / Q000502:physiology*; D009672:Notochord / Q000166:cytology; D013116:Spinal Cord / Q000166:cytology
chemical_list: C530105:Ccnd1 protein, mouse; D019938:Cyclin D1
keywords: Cell proliferation; Embryo; Mouse; Neural tube closure; Neurulation