4.8 Article

Hinge point emergence in mammalian spinal neurulation

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2117075119

关键词

neural tube; posterior neuropore; hinge points; zippering; computational model

资金

  1. Swiss National Science Foundation Sinergia Grant [CRSII5-170930]
  2. Utrecht Selective Life Sciences ExtraCurricular Track travel grant (Utrecht University, The Netherlands)
  3. Swiss-European Mobility Programme scholarship
  4. Howard Hughes Medical Institute
  5. Eidgenossche Technische Hochschule (ETH) Zurich under ETH Independent Investigators' Research Awards [ETH03 10-3]
  6. Swiss National Science Foundation (SNF) [CRSII5_170930] Funding Source: Swiss National Science Foundation (SNF)

向作者/读者索取更多资源

This study investigates the biomechanical mechanism of mammalian neural tube formation using a mechanical finite element model. The researchers achieved neural tube closure by simulating mesoderm expansion, nonneural ectoderm expansion, and neural plate adhesion to the notochord. They propose that the biomechanical force for dorsolateral hinge point formation comes from zippering.
Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the posterior neuropore changes over time, first showing a median hinge point, then both the median hinge point and dorsolateral hinge points, followed by dorsolateral hinge points only. The biomechanical mechanism of hinge point formation in the mammalian neural tube is poorly understood. Here we employ a mechanical finite element model to study neural tube formation. The computational model mimics the mammalian neural tube using microscopy data from mouse and human embryos. While intrinsic curvature at the neural plate midline has been hypothesized to drive neural tube folding, intrinsic curvature was not sufficient for tube closure in our simulations. We achieved neural tube closure with an alternative model combining mesoderm expansion, nonneural ectoderm expansion, and neural plate adhesion to the notochord. Dorsolateral hinge points emerged in simulations with low mesoderm expansion and zippering. We propose that zippering provides the biomechanical force for dorsolateral hinge point formation in settings where the neural plate lateral sides extend above the mesoderm. Together, these results provide a perspective on the biomechanical and molecular mechanism of mammalian spinal neurulation.

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