1. Analysis and Digital Reconstruction of Drosophila Brain Development
Digital 3D models play an increasingly important role in neuroscience. Representing three-dimensional scaffolds in which functional 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.
We are generating 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 connectivity. Axonal and dendritic arborizations, together with glial cells, establish morphologically distinct neuropile compartments that are visible from the late embryo towards the adult. Compartments along with lineages and their tracts form a stereotyped pattern that are captured in digital models. The goal of this modeling project is to provide a tool shared with the community, allowing one to exploit the Drosphila brain more efficiently for developmental-genetic and functional questions.
2. Genetic Mechanism of Neurite Branching in the Drosophila Brain
Understanding the molecular mechanisms of neurite branching is important not only for the neuroscientist interested in understanding brain development, but also for the clinician following the rapidly evolving therapeutic approaches that utilize transplants of undifferentiated neurons for neurodegenerative diseases, such as Parkinson or Alzheimer s disease. For such transplants to be effective, it would greatly help if one could manipulate the manner in which the donor neurons interact with the host s microenvironment and, in response, form branched neurites that become integrated within the hosts circuitry. Drosophila provides an excellent model system to address neurite branching at a high level of resolution because the wealth of molecular-genetic tools and the fact that neurons of the brain fall into lineages that are generated from a relatively small number of stem cell-like neuroblasts. The nerve fiber tracts of each lineage undergo a characteristic pattern of branching, which makes it possible to recognize and work with them. We are focusing on the interaction between axons and glia as a mechanism to set specific branch points; furthermore, we are investigating the role of membrane bound protein complexes, such as the Par/Baz complex and the Cadherin-Catenin complex, in neurite branching.
3. Stem Cells and their Niches in Invertebrate Model Systems
More than any other model organism, Drosophila has yielded insight into the interaction between self renewing stem cells and their microenvironment (stem cell niches). We are studying stem cell-niche development/interaction in the Drosophila blood system, the intestine, and the brain. In the brain, stem cells (neuroblasts) persist throughout metamorphosis, and we are focusing on the role of specific glial cell populations that enclose neuroblasts. In addition, we are looking at neuronal renewal in a basal bilaterian, the flatworm Macrostomum lignano. In flatworms, tissues, including the brain, grow by incorporating freely moving, totipotent stem cells, called neoblasts. To lay the groundwork for a molecular analysis of neoblast recruitment and neural differentiation, we are investigating embryonic and postembryonic brain development in Macrostomum.
