Apoptosis is not required for mammalian neural tube closure

Valentina Massa, Dawn Savery, Patricia Ybot-Gonzalez, Elisabetta Ferraro, Anthony Rongvaux, Francesco Cecconi, Richard Flavell, Nicholas D E Greene, Andrew J. Copp

Research output: Contribution to journalArticlepeer-review


Apoptotic cell death occurs in many tissues during embryonic development and appears to be essential for processes including digit formation and cardiac outflow tract remodeling. Studies in the chick suggest a requirement for apoptosis during neurulation, because inhibition of caspase activity was found to prevent neural tube closure. In mice, excessive apoptosis occurs in association with failure of neural tube closure in several genetic mutants, but whether regulated apoptosis is also necessary for neural tube closure in mammals is unknown. Here we investigate the possible role of apoptotic cell death during mouse neural tube closure. We confirm the presence of apoptosis in the neural tube before and during closure, and identify a correlation with 3 main events: bending and fusion of the neural folds, postfusion remodeling of the dorsal neural tube and surface ectoderm, and emigration of neural crest cells. Both Casp3 and Apaf1 null embryos exhibit severely reduced apoptosis, yet neurulation proceeds normally in the forebrain and spine. In contrast, the mutant embryos fail to complete neural tube closure in the midbrain and hindbrain. Application of the apoptosis inhibitors z-Vad-fmk and pifithrin-α to neurulation-stage embryos in culture suppresses apoptosis but does not prevent initiation or progression of neural tube closure along the entire neuraxis, including the midbrain and hindbrain. Remodeling of the surface ectoderm to cover the closed tube, as well as delamination and migration of neural crest cells, also appear to be normal in the apoptosis-suppressed embryos. We conclude that apoptosis is not required for neural tube closure in the mouse embryo.

Original languageEnglish
Pages (from-to)8233-8238
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
Publication statusPublished - May 19 2009


  • Cell death
  • Embryo
  • Morphogenesis
  • Neurulation

ASJC Scopus subject areas

  • General


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