Early neural cell death: Determined to die.

摘要

The development of a complex multi-cellular organism from a zygote requires coordinated processes of cell proliferation, differentiation and death. Programmed cell death (PCD) refers to cell death that is regulated by a genetic program. The majority of PCD occurring in metazoan development proceeds through apoptosis, a highly conserved and morphologically distinct process.; PCD plays important roles in the formation of various tissues and organs in vertebrate development. Two types of PCD occur during the development of the nervous system. 50% of all differentiated neurons undergo apoptosis, a process essential for the establishment of proper neuronal connections. This is referred as neurotrophic cell death, triggered by limited amounts of trophic support released from the target cells these neurons innervate. The second type of PCD takes place within populations of proliferating and undifferentiated neural progenitors, known as early neural cell death. Unlike neurotrophic cell death, the regulation and role of early neural cell death is not well-understood.; Early neural cell death occurs in the fish, frog, chick and mouse. This thesis addresses the requirement and regulation of early neural cell death in the South African clawed frog, Xenopus laevis. I inhibited early neural cell death during the initial stages of neural development known as primary neurogenesis, and demonstrated that early neural cell death is required for normal primary neurogenesis in Xenopus.; The similarity between the pattern of early neural cell death and that of neuronal differentiation suggests that the two processes are tightly connected. Here, I showed that early neural cell death is sensitive to the level of neurogenesis mediated by XNgnr1, which controls neuronal determination. This indicates that early neural cell death is regulated, at least in part, by XNgnr1. My studies further suggest that early neural cell death occurs as a corrective response to high levels of XNgnr1 activity, which result in abnormal neurogenesis.