Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis

In vertebrates the neural tube, like most of the embryonic organs, shows di screet areas of programmed cell death at several stages during development. In the chick embryo, cell death is dramatically increased in the developin g nervous system and other tissues when the midline cells, notochord and fl oor plate, are prevented from forming by excision of the axial-paraxial hin ge (APH), i.e. caudal Hensen's node and rostral. primitive streak, at the 6 -somite stage (Charrier, J. B., Teillet, M.-A., Lapointe, R and Le Douarin, N. M. (1999). Development 126, 4771-4783). In this paper we demonstrate th at one day after APH excision, when dramatic apoptosis is already present i n the neural tube, the latter can be rescued from death by grafting a notoc hord or a floor plate fragment in its vicinity. The neural tube can also be recovered by transplanting it into a stage-matched chick embryo having one of these structures. In addition, cells engineered to produce Sonic hedgeh og protein (SHH) can mimic the effect of the notochord and floor plate cell s in in situ grafts and transplantation experiments. SHR can thus counterac t a built-in cell death program and thereby contribute to organ morphogenes is, in particular in the central nervous system.