The non-canonical Wnt-PCP pathway shapes the caudal neural plate

The last stage of neural tube (NT) formation involves closure of the caudal neural plate (NP), an embryonic structure formed by neuromesodermal progenitors and newly differentiated cells that becomes incorporated into the NT. Here, we show in mouse that, as cell specification progresses, neuromesodermal progenitors and their progeny undergo significant changes in shape prior to their incorporation into the NT. The caudo-rostral progression towards differentiation is coupled to a gradual reliance on a unique combination of complex mechanisms that drive tissue folding, involving pulses of apical actomyosin contraction and planar polarised cell rearrangements, all of which are regulated by the Wnt-PCP pathway. Indeed, when this pathway is disrupted, either chemically or genetically, the polarisation and morphology of cells within the entire caudal NP is disturbed, producing delays in NT closure. The most severe disruptions of this pathway prevent caudal NT closure and result in spina bifida. In addition, a decrease in Vangl2 gene dosage also appears to promote more rapid progression towards a neural fate, but not the specification of more neural cells.This work was supported by grants from the Instituto de Salud Carlos III (PS09/00050, CP08/00111, CPII14/00033, PI14/01075 and PI17/00693 to P.Y.-G.) co-financed by the European Regional Development Fund “A way to achieve Europe”; the Andalusian Health Service, Junta de Andalucia (Servicio Andaluz de Salud, Junta de Andalucia; PI-0438-2010 to P.Y.-G.); the Andalusian Regional Ministry of Economy, Science and Innovation (Consejerıa de Econom ́ ıa, Innovacio ́ ́ń, Ciencia y Empleo, Junta de Andalucıá ́; P11-cts-7634 to P.Y.-G.); the National Institutes of Health (R01 HD044750 to L.A.D.); and the National Science Foundation (CMMI-1100515 to L.A.D.). In addition, D.S.V. was supported by the “Biomechanics in Regeneration” Training Program from the National Institute of Biomedical Imaging and Bioengineering (BiRM T32 EB003392)