A Pulse of the Drosophila Hox Protein Abdominal-A Schedules the End of Neural Proliferation via Neuroblast Apoptosis

Abstract

Postembryonic neuroblasts are stem cell-like precursors that generate most neurons of the adult Drosophila central nervous system (CNS). Their capacity to divide is modulated along the anterior-posterior body axis, but the mechanism underlying this is unclear. We use clonal analysis of identified precursors in the abdomen to show that neuron production stops because the cell death program is activated in the neuroblast while it is still engaged in the cell cycle. A burst of expression of the Hox protein Abdominal-A (AbdA) specifies the time at which apoptosis occurs, thereby determining the final number of progeny that each neuroblast generates. These studies identify a mechanism linking the Hox axial patterning system to neural proliferation, and this involves temporal regulation of precursor cell death rather than the cell cycle.

Guidance Molecules in Axon Pruning and Cell Death

“…The physiological meaning of apoptosis in neural progenitors has remained largely unexplored for a long time (Bello et al 2003;Kuan et al 2000). 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.…”

“…Region-specific apoptosis of neural progenitors was also proposed recently as a patterning mechanism to restrict in time and space the size of distinct neural stem cell lineages in Drosophila CNS, thereby playing an essential role in the spatial patterning of the nervous system (Bello et al 2003).…”

Insights into neural stem cell biology from flies

“…However, the end of abdominal neuroblast proliferation is one aspect of larval neurogenesis that has begun to be understood. It has been shown that during the third larval instar, abdominal neuroblasts undergo programmed cell death (Bello et al 2003). When an abdominal neuroblast is made deficient for the three proapoptotic genes, head involution defective, grim and reaper, it persists throughout larval life, generating many more progeny than normal.…”

Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons

“…In Drosophila there are 2 ways to regulate the cell numbers in early neural development. One is the cell autonomous control during neurogenesis just after the cell fate determination (8)(9)(10)(11). The other, the cell nonautonomous control is less documented.…”