Department of Biology
Yale Uninversity

  The nervous systems of many invertebrates are composed of uniquely specified and individually identifiable neurons. Dr Keshishian is currently interested in the development of identified neurons in insect embryos, where they can be directly studied and manipulated. One topic of interest is how embryonic neurons establish their characteristic axonal trajectories in the CNS and the periphery, and as a result project to their appropriate central and peripheral targets. Dr Keshishian has studied the role that pioneer neurons and guidepost or landmark cells play in controlling the morphology of peripheral nerves. An important problem is to identify how the growing end of an axon recognizes and responds to guidance cues and other surface features in the embryonic landscape. Dr Keshishian's other ineterest is how exploring growth cones find their appropriate synaptic targets.

More recently, Dr Keshishian has begun to study how Drosophila motoneurons find their appropriate peripheral targets on the embryonic skeletal musculature. Drosophila is particularly well suited for an analysis of this sort, as there is a fixed number of singly identifiable muscle fibers per segment, where each of the 30 fibers per side receives multiple motoneuronal inputs. When the embryonic growth cones contact their target muscle fibers, they make highly stereotypic projections on their surfaces, and may be responding to specific surface recognition molecules expressed by the target cells. In the course of about one hour, the growth cones establish the basic mature synaptic phenotype, including stereotyped branch anatomy, projection trajectories, and transmitter expression. Dr Keshishian is currently employing both genetic and laser micromanipulation methods to examine the cellular mechanisms governing this remarkably precise form of synapto-genesis.

Work in the lab involves intracellular physiology of embryonic neurons, micromanipulation, embryo and tissue culture, immunocytochemistry, genetics, and digital optical microscopy.

Further Reading

Chiba, A., P. Snow, H. Keshishian, Y. Hotta (1995). Fasciclin III as a synaptic recognition molecule in Drosophila. Nature 374:166-168.

Jarecki, J. and H. Keshishian (1995). The role of neural activity during synapto-genesis in Drosophila. J. Neurosci. 15:8177-8190.

Keshishian, H., Broadie, K., Chiba A., and M. Bate (1996). The Drosophila neuro-muscular junction: A model system for studying synaptic development and function. Ann. Review Neurosci. 19:545-575.