3D Digital Modeling of the Drosphila Brain

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Digital 3D models play an increasingly important role in neuroscience. Representing three-dimensional scaffolds in which functional data and gene expression data are entered and displayed graphically, the digital models become analytical tools that allow one to address neural connectivity and function, as well as gene function and gene interactions. This grant application proposes to generate a series of standardized digital atlas models of the developing Drosophila brain, a system used by many to investigate the genetic mechanism controlling the formation and function of neuronal circuits. The fly brain is formed by an invariant set of neuroblast lineages which represent structural units in terms of cell body location, axonal projection, and (to an extent that will be addressed in this proposal) connectivity. Axonal and dendritic arborizations, establish morphologically distinct neuropile compartments that are visible from the late embryo towards the adult. Compartments and lineages form a stereotyped pattern that will be captured in the proposed digital models. Having in mind their usefulness for us and others, as well as feasibility, the following models are proposed: (1) early embryonic neuroblast map, (2) late embryonic primary lineages in relation to evolving neuropile, (3) late larval secondary lineages in relation to neuropile compartments, (4) evolving secondary tract systems and neuropile compartments of the pupa. These models represent an integrated series because the "genetic address" of each neuroblast, defined by the known sets of genes expressed in the early embryonic neuroblast map, will be linked to the population of neurons and their axons modeled for the late embryo, larva and pupa. The goal of this modeling project is to provide a tool shared with the community, allowing to exploit the Drosphila brain more efficiently for developmental-genetic and functional questions. Models of neural lineages will make it possible to phrase specific experiments and to interpret mutant phenotypes.