Cenci, C.; (2004) Regulation of segment-specific neurogenesis in Drosophila. Doctoral thesis , University of London.

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Abstract

Following Drosophila embryogenesis, the morphology of the central nervous system (CNS) becomes dramatically remodelled to reflect the different locomotive and sensory requirements of the adult relative to the larva. The late embryonic onset of segment-to-segment differences in the number and mitotic capacity of neural stem cell-like precursors (termed neuroblasts: NBs) is critical to this resculpting process. My studies address the roles of homeodomain and other transcription factors in regulating thoracic and abdominal-specific patterns of neurogenesis, focusing on one embryonic and one larval example. In the embryo, dividing NBs sequentially express a temporal series of transcription factors required to link birth-order to neuronal identity. The study of a group of neurons expressing the early NB-sublineage determinant Hunchback in a thorax-specific pattern (termed the THBs) was initiated. I developed a lineage- labelling method to show that the THB-producing NBs appear to undergo a delay in their sub-lineage transition from Hunchback-positive to negative status, relative to most other NBs. Importantly, gene skipping in the canonical transcription factor series is also observed. Genetic analysis reveals that this thorax-specific pattern of neurogenesis requires homothorax but surprisingly not the thoracic Hox genes. However, in the abdomen, the Hox genes Ultrabithorax and abdominalA are required to suppress the THB phenotype. In the larva, clonal analysis and CNS-specific mutants were used to test several candidate factors potentially regulating NB divisions. This approach identified critical roles for Polycomb group genes and the transcription factor Grainyhead (Grh). I find that Grh, previously implicated as the ultimate NB-sublineage determinant in the embryo, has a differential effect on larval neurogenesis in the thorax versus the abdomen. Individual grh NB lineages in the thorax are smaller than wild type and stop dividing prematurely whereas those in the abdomen are larger and divide for an abnormally long period. Underlying the latter effect is an inability to respond to the normal NB-apoptosis inducing burst of the Hox protein AbdominalA. Thus, these studies identify Grh as a context-factor for Hox function in the larval NBs, linking late but not early AbdominalA expression with NB-apoptosis.

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