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Chihiro HAMA, Ph. D. 
One
of the most tantalizing questions in the field of neurobiology is how
neural circuits of exquisite complexity are generated during nervous system
development. Human brains consist of 1010 neurons,
and each neuron projects an axon that extends along a predetermined pathway
before finally finding its specific synaptic partner from myriad dendrites.
These processes are regulated by a number of intrinsic factors and extracellular
cues, which may be expressed in subsets of cells or localized to limited
intracellular regions. To improve our understanding of the molecular mechanisms
underlying this circuit formation, we have conducted a mutant screen using
fruit flies to identify the regulatory factors involved, and addressed
the issue of how vesicle transport is involved in neurite differentiation.
We
chose to study the olfactory sensory system in our mutant screen, as this
system exhibits beautiful organization in its structure. Drosophila
carries 1300 olfactory receptor neurons (ORNs) on its head appendages.
Each of these neurons projects an axon into one or two out of 50 glomeruli
in the antennal lobe, which is the first centralized olfactory processing
region in the brain. The Drosophila genome encodes about 60 odorant
receptors (ORs), and each olfactory receptor neuron expresses only a single
OR. Interestingly, axons from neurons that express a given OR precisely
converge at one or two glomeruli, suggesting that olfactory codes in the
brain are generated by a combination of glomeruli stimulated through ORs.
To
study the question of how olfactory receptor neuronal axons are specifically
targeted to the correct glomerular positions, we have isolated a number
of mutations that impair the projection of ORN axons into glomeruli. The
genes responsible for these mutant phenotypes may be involved in axon
guidance, synaptic targeting, glomerular formation or synapse formation.
We have found one mutation of particular interest, which affects the asymmetric
cell fate specification of ORNs that form pairs or clusters from single
precursors during development and, as a consequence, change synaptic targets.
It is hoped that analysis of this mutation will reveal a principle governing
glomerular organization in the antennal lobe.
We will continue to analyze other mutations, seeking to identify factors that control the projection of ORN axons and ultimately to understand more completely the molecular mechanisms underlying glomerular organization. An appreciation of basic mechanisms uncovered in the Drosophila brain may also help us to explain how the elaborate wiring of the human brain is established early in life.
