Spinal neural tube formation and regression in human embryos

Abstract

ABSTRACTFormation of the nervous system in the human spinal region involves primary and secondary neurulation, in which the neural tube forms by closure and canalisation respectively. These processes are incompletely understood, in part due to the challenge of accessing human embryos at 3-7 weeks post-conception. A growing effort is being made to recapitulate events of neurulation in organoids derived from human stem cells. Here we present findings from a series of human embryos that can provide ‘normative data’ for interpretation of organoid results. The primary neural tube shows progressive closure during Carnegie Stages (CS) 10-13, with completion at the 30 somite stage. Somites form every 7 h, compared with organoid findings that indicate a 5 h ‘segmentation clock’. Human neural plate bending morphogenesis is closely similar to that in mouse embryos. Secondary neurulation begins from CS13, with initial formation of a single lumen as in mouse, not by coalescence of multiple lumens as in chick. Termination of axial elongation occurs after downregulation ofWNT3AandFGF8in the CS15 embryonic tailbud, with a ‘burst’ of apoptosis that may remove the neuro-mesodermal progenitors. Axial length declines during tail regression, with different axial elements showing varied patterns of apoptotic removal.