Wesley B. Grueber
Department of Physiology & Cellular Biophysics
630 W. 168th Street
Physicians & Surgeons 11-451
New York, NY 10032
2007 Searle Scholar
The morphologies of dendrites and axons are the fundamental building blocks of neuronal circuits, yet how neurons attain their enormous variety of shapes remains a perplexing and poorly understood problem. Our lab is interested in how neurons acquire their type-specific morphology and how this morphology influences nervous system function. We approach this problem by studying the development of individual neurons and individual dendritic and axonal processes. We aim to identify conserved morphological principles in the nervous system (such as "tiling" see below), and then use molecular and genetic approaches to understand the mechanisms by which specific neuronal morphologies are sculpted during development.
We use as a model system a population of sensory neurons that spread dendrites in two dimensions across the body wall of Drosophila melanogaster. These neurons show diverse, yet stereotyped, morphologies and are therefore well-suited for us to study how a neuron achieves a cell-specific or class-specific branching pattern. Using this system, we can also genetically manipulate and image neuronal morphogenesis by removing or expressing genes in specific neurons. For example, we have shown that repulsive mechanisms operating between dendritic branches play a major role in guiding the characteristic "spreading" of individual dendritic arbors, as well as limit the extent of dendritic growth. When dendrites have reached an appropriate size, such repulsion ensures that dendrites of the same morphological or functional type provide complete but non-redundant coverage of the body wall. The best analogy is to simply observe how tiles cover a floor. The tiles, if laid correctly, show neither gaps nor overlaps, and thus provide efficient and full coverage. Similarly, dendrites must often tile their territory completely without gaps or overlap so as to fairly sample all information impinging on them. By identifying genes that, when disrupted, lead to defective dendrite patterning, we are beginning to unravel the molecular basis of conserved signals that give neurons their unique shapes crucial for proper nervous system functioning.
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