Contribution of apoptosis in cranial neural tube closure indicated by mouse embryo live imaging

Abstract

Many cells die during development through the process called programmed cell death (PCD). Dysregulation of apoptosis, a major form of PCD during development, leads to cranial neural tube closure (NTC) defects such as exencephaly, but the underlying mechanism has remained unclear. Observing cells undergoing apoptosis in the normal developmental process will help elucidate their nature, characteristics, and interaction with surrounding tissues. Using a newly developed transgenic mouse that stably expressed a genetically encoded FRET-based fluorescent reporter for caspase activation, we performed simultaneous time-lapse imaging of apoptosis and morphogenesis in living embryos. This analysis, based on live imaging, indicated that inhibition of caspase activation interfered with and delayed the progression of NTC in the cranial region. The analysis also revealed existence of two types of apoptotic cells during NTC. Based on these results, we propose that cell removal by caspase-mediated apoptosis facilitates NTC and ensues the completion of NTC within a limited developmental time window.