Activity regulates programmed cell death of zebrafish Rohon-Beard neurons

Programmed cell death is a normal aspect of neuronal development. Typically , twice as many neurons are generated than survive. In extreme cases, all n eurons within a-population disappear during embryogenesis or by early stage s of postnatal development. Examples of transient neuronal populations incl ude Cajal-Retzius cells of the cerebral cortex and Rohon-Beard cells of the spinal cord. The novel mechanisms that lead to such massive cell death hav e not yet been identified. We provide evidence that electrical activity regulates the cell death progr am of zebrafish Rohon-Beard cells. Activity was inhibited by reducing Na+ c urrent in Rohon-Beard cells either genetically (the macho mutation) or phar macologically (tricaine). We examined the effects of activity block on thre e different reporters of cell death: DNA fragmentation, cytoskeletal rearra ngements and cell body loss. Both the mao mutation and pharmacological bloc kade of Na+ current reduced these signatures of the cell death program. Mor eover, the mao mutation and pharmacological blockade of Na+ current produce d similar reductions in Rohon-Beard cell death. The results indicate that e lectrical activity provides signals that are required for the normal elimin ation of Rohon-Beard cells.