A role for programmed cell death during early neurogenesis in xenopus

Abstract

In vertebrates, little is known on the role of programmed cell death (PCD) occurring within the population of dividing neural precursors and newly formed neuroblasts during early neural development. During primary neurogenesis, PCD takes place within the neuroectoderm of Xenopus embryos in a reproducible stereotypic pattern, suggesting a role for PCD during the early development of the CNS. We find that the spatio-temporal pattern of PCD is unaffected in embryos in which cell proliferation has been blocked and whose neuroecotoderm contains half the normal number of cells. This shows that PCD is not dependent on cell division. It further suggests that PCD does not solely function to regulate absolute cell numbers within the neuroectoderm. We demonstrate that PCD can be reproducibly inhibited in vivo during primary neurogenesis by the overexpression of human Bcl-2. Following PCD inhibition, normal neurogenesis is disrupted, as seen by the expansion of the expression domains of XSox-2, XZicr-2, XNgnr-1, XMyT-1, and N-Tubulin, XNgnr-1 being the most affected. PCD inhibition, however, did not affect the outcome of lateral inhibition. We propose, then, that PCD regulates primary neurogenesis at the level of neuronal determination.

Guidance Molecules in Axon Pruning and Cell Death

“…The presence of significant levels of apoptosis in the proliferative zone of the mouse brain (Blaschke et al 1996), since then confirmed in other species including the human (Rakic and Zecevic 2000;Yeo and Gautier 2003), suggested that cell death is not a phenomenon exclusively restricted to postmitotic neurons, but this did not necessarily imply that apoptosis regulation was linked to brain patterning. A first important hint came from the analysis of caspase gene invalidation in mutant mice: The mutants invalidated for pro-apoptotic genes Caspase-3, Caspase-9, and Apaf1 present a similar phenotype, consisting in a drastic reduction in early cerebral apoptosis and an inappropriate amplification of specific populations of neural progenitors, resulting in brain exencephaly and neural overgrowth (Cecconi et al 1998;Hakem et al 1998;Kuida et al 1996;Kuida et al 1998;Pompeiano et al 2000).…”

“…In vertebrates, the contribution of apoptotic processes to neural regional patterning remains unclear at this stage, although the patterns of neural progenitor apoptosis are strikingly dynamic in time and space (Blaschke et al 1996;Rakic and Zecevic 2000;Yeo and Gautier 2003). On the other hand, several extracellular cues have been recently identified that control early neural cell death.…”

To proliferate or to die: role of Id3 in cell cycle progression and survival of neural crest progenitors

“…Under normal conditions, TUNEL staining is low or absent during gastrulation and neurulation, probably due to the rapid degradation of apoptotic cells with a turnover time of 1 h or less (Jacobson et al 1997;Hensey and Gautier 1998;Yeo and Gautier 2003). Cell cycle inhibition slows down the rate at which dying cells are degraded, thus allowing more cells to be detected by TUNEL at a given time (Yeo and Gautier 2003).…”

“…Cell cycle inhibition slows down the rate at which dying cells are degraded, thus allowing more cells to be detected by TUNEL at a given time (Yeo and Gautier 2003). Id3-depleted embryos clearly showed increased TUNELpositive staining on the injected side, possibly due to a blockade of the cell cycle and subsequent cell death.…”

Relationships between calpains and glutamate- or kainate-induced apoptosis in Xenopus laevis tadpoles

“…This phenomenon involved the expression of several developmental genes such as Xotx2 or Xrx1 [48]. In X. laevis, Yeo and Gautier showed that PCD regulated the primary neural determination [49]. A third wave of apoptosis was then observed on late neurulation, when axons develop from maturating neurones.…”