By visualizing the dynamics of apoptosis in living mouse embryos, Yamaguchi et al. reveal that cell death helps drive the morphogenetic movements required for neural tube closure (NTC).
NTC is a vital early step in the development of the central nervous system. A flat group of cells called the neural plate bends in the middle so that the sides of the plate curve around to meet and fuse with each other, forming the neural tube. Many mouse embryos lacking key apoptosis proteins, such as Apaf-1 or Caspase-3, show defects in NTC in their cranial region, but how cell death contributes to this process is unclear.
Yamaguchi et al. generated transgenic mice expressing a FRET-based apoptotic reporter whose signal is decreased when activated caspases cleave the link between two fluorescent proteins. Using this reporter, the researchers identified two types of apoptotic cells in embryonic brains undergoing NTC. Some cells died and fragmented rapidly, whereas others—particularly near the tips of the folding neural plate—persisted for longer without breaking apart.
Both types of apoptotic cells were absent from mouse embryos lacking Apaf-1 and Caspase-3. In these animals, neural plate bending was reduced, thereby delaying NTC. Senior authors Yoshifumi Yamaguchi and Masayuki Miura think that the death, and subsequent extrusion, of cells from the tips of the neural plate may generate forces that help to shape the developing tissue and facilitate cranial NTC. Alternatively, the two types of apoptotic cells may direct this developmental process by sending different signals to their surviving neighbors.