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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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