IS PROGRAMMED CELL-DEATH REQUIRED FOR NEURAL-TUBE CLOSURE

Programmed cell death (PCD) plays an important part in animal developm ent. It is responsible for eliminating the cells between developing di gits, for example, and is involved in hollowing out solid structures t o create cavities (reviewed in [1,2]). There are many cases, however, where PCD occurs in developing tissues but its function is unknown. Im portant examples are seen during the folding, pinching off, and fusion of epithelial sheets during vertebrate morphogenesis, as in the forma tion of the neural tube and lens vesicle [2]; PCD is an invariable acc ompaniment to these processes, but it is unclear whether it is require d 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 t o act in a proteolytic cascade, cleaving one another and key intracell ular proteins to kill the cell in a controlled way [3,4]. Inhibitors o f caspases are, therefore, potential tools for studying the roles of P CD during animal development [5,6]. Here, we show that peptide caspase inhibitors block neural tube closure in explanted chick embryos, sugg esting that PCD is required for this crucial developmental process. (C ) Current Biology Ltd.