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Is programmed cell death required for neural tube closure?

1997; Elsevier BV; Volume: 7; Issue: 4 Linguagem: Inglês

10.1016/s0960-9822(06)00125-4

1879-0445

Miguel Weil, Michael D. Jacobson, Martin Raff,

Retinal Development and Disorders

Programmed cell death (PCD) plays an important part in animal development. It is responsible for eliminating the cells between developing digits, for example, and is involved in hollowing out solid structures to create cavities (reviewed in [1Jacobson MD Weil M Raff MC Programmed cell death in animal development.Cell. 1997; 88: 347-354Abstract Full Text Full Text PDF PubMed Scopus (2340) Google Scholar, 2Glucksmann A Cell deaths in normal vertebrate ontogeny.Biol Rev. 1951; 26: 59-86Crossref PubMed Scopus (864) Google Scholar]). There are many cases, however, where PCD occurs in developing tissues but its function is unknown. Important examples are seen during the folding, pinching off, and fusion of epithelial sheets during vertebrate morphogenesis, as in the formation of the neural tube and lens vesicle [[2]Glucksmann A Cell deaths in normal vertebrate ontogeny.Biol Rev. 1951; 26: 59-86Crossref PubMed Scopus (864) Google Scholar]; PCD is an invariable accompaniment to these processes, but it is unclear whether it is required for the processes to occur or is just an unavoidable consequence of them. There is increasing evidence that PCD in animals is mediated by a family of cysteine proteases, known as caspases, which are thought to act in a proteolytic cascade, cleaving one another and key intracellular proteins to kill the cell in a controlled way [3Martin SJ Green DR Protease activation during apoptosis: death by a thousand cuts?.Cell. 1995; 82 (95360977): 349-352Abstract Full Text PDF PubMed Scopus (1241) Google Scholar, 4Alnemri ES Livingston DJ Nicholson DW Salvesen G Thornberry NA Wong WW Yuan J Human ICE/CED3 protease nomenclature.Cell. 1996; 87: 171Abstract Full Text Full Text PDF PubMed Scopus (2079) Google Scholar]. Inhibitors of caspases are, therefore, potential tools for studying the roles of PCD during animal development [5Milligan CE Prevette D Yaginuma H Homma S Cardwell C Fritz LC et al.Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro.Neuron. 1995; 15 (95374793): 385-393Abstract Full Text PDF PubMed Scopus (293) Google Scholar, 6Jacobson MD Weil M Raff MC Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death.J Cell Biol. 1996; 133 (96251671): 1041-1051Crossref PubMed Scopus (358) Google Scholar]. Here, we show that peptide caspase inhibitors block neural tube closure in explanted chick embryos, suggesting that PCD is required for this crucial developmental process.