Talk:Neural Tube Closure Movie

From Embryology

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

J Cell Biol. 2011 Dec 12;195(6):1047-60. doi: 10.1083/jcb.201104057.

Yamaguchi Y, Shinotsuka N, Nonomura K, Takemoto K, Kuida K, Yosida H, Miura M. Source Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.


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.

PMID 22162136

Caspases and matrix metalloproteases facilitate collective behavior of non-neural ectoderm after hindbrain neuropore closure

BMC Dev Biol. 2018 Jul 31;18(1):17. doi: 10.1186/s12861-018-0175-3.

Shinotsuka N1, Yamaguchi Y2,3, Nakazato K4, Matsumoto Y1, Mochizuki A4,5, Miura M6.

Abstract BACKGROUND: Mammalian brain is formed through neural tube closure (NTC), wherein both ridges of opposing neural folds are fused in the midline and remodeled in the roof plate of the neural tube and overlying non-neural ectodermal layer. Apoptosis is widely observed from the beginning of NTC at the neural ridges and is crucial for the proper progression of NTC, but its role after the closure remains less clear.

RESULTS: Here, we conducted live-imaging analysis of the mid-hindbrain neuropore (MHNP) closure and revealed unexpected collective behavior of cells surrounding the MHNP. The cells first gathered to the closing point and subsequently relocated as if they were released from the point. Inhibition of caspases or matrix metalloproteases with chemical inhibitors impaired the cell relocation.

CONCLUSIONS: These lines of evidence suggest that apoptosis-mediated degradation of extracellular matrix might facilitate the final process of neuropore closure.

KEYWORDS: Apoptosis; Caspases; Live-imaging; Matrix metalloproteases; Neural tube closure PMID: 30064364 PMCID: PMC6069860 DOI: 10.1186/s12861-018-0175-3