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Publication : Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure.

First Author  Yamaguchi Y Year  2011
Journal  J Cell Biol Volume  195
Issue  6 Pages  1047-60
PubMed ID  22162136 Mgi Jnum  J:178905
Mgi Id  MGI:5300618 Doi  10.1083/jcb.201104057
Citation  Yamaguchi Y, et al. (2011) Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure. J Cell Biol 195(6):1047-60
abstractText  Many cells die during development, tissue homeostasis, and disease. Dysregulation of apoptosis leads to cranial neural tube closure (NTC) defects like exencephaly, although the mechanism is unclear. Observing cells undergoing apoptosis in a living context could help elucidate their origin, behavior, and influence on surrounding tissues, but few tools are available for this purpose, especially in mammals. In this paper, we used insulator sequences to generate a transgenic mouse that stably expressed a genetically encoded fluorescence resonance energy transfer (FRET)-based fluorescent reporter for caspase activation and performed simultaneous time-lapse imaging of apoptosis and morphogenesis in living embryos. Live FRET imaging with a fast-scanning confocal microscope revealed that cells containing activated caspases showed typical and nontypical apoptotic behavior in a region-specific manner during NTC. Inhibiting caspase activation perturbed and delayed the smooth progression of cranial NTC, which might increase the risk of exencephaly. Our results suggest that caspase-mediated cell removal facilitates NTC completion within a limited developmental window.
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