The programmed cell death (PCD) of developing cells is considered an essential adaptive process that evolved to serve diverse roles. We review the putative adaptive functions of PCD in the animal kingdom with a major focus on PCD in the developing nervous system. Considerable evidence is consistent with the role of PCD in events ranging from neurulation and synaptogenesis to the elimination of adult-generated CNS cells. The remarkable recent progress in our understanding of the genetic regulation of PCD has made it possible to perturb (inhibit) PCD and determine the possible repercussions for nervous system development and function. Although still in their infancy, these studies have so far revealed few striking behavioral or functional phenotypes.

Adaptive roles of programmed cell death during nervous system development.

A comparative framework for understanding the biological principles of adult neurogenesis.

The mode of embryonic and larval development and the ethology of metamorphosis in the spider crab and the American lobster are very different, and we took advantage of this to compare neuronal development in the two species. The goals of this study were to discover whether the differences in the maturation of the neuromuscular system in the pereopods and the metamorphic changes of motor behavior between the two species are reflected at the level of the developing nervous system ('neurometamorphosis'). Furthermore, we wanted to broaden our understanding of the mechanisms that govern neuronal development in arthropods. Proliferation of neuronal stem cells in thoracic neuromeres 4-8 of the lobster Homarus americanus and the crab Hyas araneus was monitored over the course of embryonic and larval development using the in vivo incorporation of bromodeoxyuridine (BrdU). Neuropil structure was visualized using an antibody against Drosophila synapsin. While proliferation of neuronal precursors has ceased when embryogenesis is 80 % complete (E80%) in the lobster thoracic neuromeres, proliferation of neuroblasts in the crab persists throughout embryonic development and into larval life. The divergent temporal patterns of neurogenesis in the two crustacean species can be correlated with differences in larval life style and in the degree of maturation of the thoracic legs during metamorphic development. Several unusual aspects of neurogenesis reported here distinguish these crustaceans from other arthropods. Lobsters apparently lack a postembryonic period of proliferation in the thoracic neuromeres despite the metamorphic remodeling that takes place in the larval stages. In contrast, an increase in mitotic activity towards the end of embryonic development is found in crabs, and neuroblast proliferation persists throughout the process of hatching into the larval stages. In both E20% lobster embryos and mid-embryonic crabs, expression of engrailed was found in a corresponding set of neurons and putative glial cells at the posterior neuromere border, suggesting that these cells have acquired similar specific identities and might, therefore, be homologous. None of the BrdU-labeled neuroblasts (typically 6-8 per hemineuromere over a long period of embryogenesis) was positive for engrailed at this and subsequent stages. Our findings are discussed in relation to the spatial and temporal patterns of neurogenesis in insects.

Neurogenesis in the thoracic neuromeres of two crustaceans with different types of metamorphic development

Ontogeny of the ventral nerve cord in malacostracan crustaceans: a common plan for neuronal development in Crustacea, Hexapoda and other Arthropoda?

The Drosophila central brain is composed of thousands of neurons that derive from approximately 100 neuroblasts per hemisphere. Functional circuits in the brain require precise neuronal wiring and tight control of neuronal numbers. How this accurate control of neuronal numbers is achieved during neural development is largely unclear. Specifically, the role of programmed cell death in control of cell numbers has not been studied in the central brain neuroblast lineages. Here, we focus on four postembryonic neuroblast lineages in the central brain identified on the basis that they express the homeobox gene engrailed (en). For each lineage, we determine the total number of adult-specific neurons generated as well as number and pattern of en-expressing cells. We then demonstrate that programmed cell death has a pronounced effect on the number of cells in the four lineages; approximately half of the immature adult-specific neurons in three of the four lineages are eliminated by cell death during postembryonic development. Moreover, we show that programmed cell death selectively affects en-positive versus en-negative cells in a lineage-specific manner and, thus, controls the relative number of en-expressing neurons in each lineage. Furthermore, we provide evidence that Notch signaling is involved in the regulation of en expression. Based on our findings, we conclude that lineage-specific programmed cell death plays a prominent role in the generation of neuronal number and lineage diversity in the Drosophila brain.

/pdf/lineage-specific-cell-death-in-postembryonic-brain-p4ivdbj7be.pdf

Lineage-specific cell death in postembryonic brain development of Drosophila

Postembryonic neurogenesis leads to a dramatic increase in the number of functional neurons within the segmental ganglia of the moth, Manduca sexta. These adult-specific neurons are generated during larval life by segment-specific arrays of individually identifiable stem cells, or neuroblasts (Nbs). By the end of the feeding larval stage, each Nb has generated a discrete nest of progeny, which ranges in size from less than 10 to more than 70 progeny. The sizes of these identifiable nests of progeny vary in a segment-specific manner, with the thoracic nests containing a greater number of progeny compared with their homologues in the simpler abdominal ganglia. In order to describe those factors that influence the size of the post-embryonic neuronal lineages, we examined the spatial and temporal pattern of postembryonic neurogenesis in the segmental ganglia of Manduca. The rates at which the identifiable nests accumulated progeny were estimated by counting the number of progeny within the nests, using sectioned material isolated from animals at stages ranging from embryonic hatching until the end of the feeding larval stage. All of the postembryonic Nbs began to generate progeny at around the time of the molt to the third larval instar. Each nest added progeny at a rate that was a characteristic of its identity and segment of origin. Although all of the nests within the thorax continued to accumulate progeny throughout the feeding larval stage, several of the abdominal nests showed little or no growth following the molt to the fifth larval instar. The thymidine analog 5-bromo 2-deoxyuridine (5-BrdU) was used to estimate the mitotic rates of the identifiable Nbs. The number of labeled progeny within a nest 24 h after application of 5-BrdU ranged from a low of 1 to 2 to a high of 11 to 13 labeled cells. In some instances there was a good correlation between the estimated mitotic rate of an identified Nb and the rate of growth of its associated nest of progeny. However, several of the identifiable nests accumulated progeny at a slower rate than predicted based on the estimated mitotic rate of the Nb. Cell death appears to be responsible for slowing the growth of the nests during the feeding larval stage. We estimate that 10% to 70% of the neurons generated during the feeding larval stage degenerate within 24 h of their birth. The level of cell death observed within a nest was dependent on both its identity and its segment of origin.

Jae Bum Kim

Papers

Postembryonic neurogenesis in the central nervous system of the tobacco hornworm, Manduca sexta. III. Spatial and temporal patterns of proliferation.