Bruce Oakley - US grants

The taste bud is a useful model for the study of nerve-epithelial interactions during development and regeneration. Taste buds are notable because they have a trophic dependence upon their nerve supply---denervated taste buds will degenerate, but will reform if the nerve regenerates. This project examines the development and regeneration of taste buds and nerves in the tongue of rats and gerbils. Studies of Regeneration: Can gustatory axons find or be attracted to their proper locations if the axons return to the tongue by an abnormal route of entry? We will use an excess of gustatory axons to determine whether hyperinnervation of taste buds occurs and whether the gustatory epithelium has a hidden capacity to form more taste buds or receptor cells. Competitive interactions between two gustatory nerves, both native and foreign to the region, will be examined. Studies of Development: We will examine the development of rodent taste buds to determine if a nerve supply is necessary for the initial formation of taste buds, and whether there is a critical period in establishing gustatory competence. We will also determine whether embryonic regulation can occur in a region previously containing gustatory epithelium and whether the absence of target gustatory epithelium in development leads to neuronal cell death. We will evaluate the residual trophic competence of gustatory epithelium and gustatory nerves after a developmental history of reduced nerve-epithelial interactions which has led to a permanent failure of taste bud development. In summary we will use electrophysiological and morphological assays to reveal some of the important principles which facilitate receptor and neuronal development and regeneration.

This award provides funds for the establishment of a Research Training Group in Development of the Nervous System. The faculty group is a mixture of outstanding senior and junior investigators who come from a variety of disciplinary backgrounds and work with a variety of organisms, but share a common interest in development of the nervous system. The research programs in which trainees will participate are aimed at three problems central to the development of all nervous systems: neurogenesis, axonal navigation, and synaptogenesis. The funds will provide stipends for graduate students and postdoctoral fellows, will support research participation by undergraduate students, will defray part of the cost of the trainees' research and will enable the trainees to attend scientific meetings. In addition, funds will be used to purchase specialized research equipment to be used by trainees, and to bring experts from other research and academic institutions to aid in a summer laboratory and lecture course for trainees. In recent years, remarkable advances in the use of genetics, biochemistry, and microscopy have led to significant new knowledge about the development of multicellular organisms. Despite this, much remains to be learned about development and, in particular, about the mechanisms of key problems posed by the development of many different tissues and structures. These include the differentiation of cell types, the basis of cell-cell recognition, and the migration of cells during development. In this respect, some of the most exciting opportunities and, at the same time, most difficult challenges are presented by developmental studies of animal nervous systems, which typically contain a large variety of cell types and extend throughout the animal. Successful research in this area requires a mixture of diverse intellectual and experimental skills not often taught in traditional neuroscience programs. This award will provide funds for the training of young neuroscientists who have the multiple skill needed to attack one of the last great frontiers of modern biology.

9413211 Oakley This award renews support of a joint training effort of 15 faculty from six departments in the Schools of Arts and Sciences, of Medicine and of Dentistry at the University of Michigan, Ann Arbor. The theme of this Research Training Group (RTG) is developmental neurobiology. Faculty and student research emphasize three aspects of the development of the nervous system: neurogenesis, axonal navigation, and synaptogenesis. The research addresses these issues in a variety of organisms, including invertebrates, fish, birds and mammals using a variety of techniques from cell and molecular biology. The RTG sponsors training at all three post-secondary levels. Besides opportunities for student research, RTG faculty have created new courses at both the undergraduate and graduate level. Graduate students are selected from students who apply to one of two departmental Ph.D. programs or an interdepartmental Neuroscience Ph.D. program, and receive support for up to three years. Postdoctoral fellows are selected for one year of support from among candidates proposed by participating faculty. Undergraduates are sponsored during both the academic year and summer term. Participants in the summer research program are recruited nationally. The level of involvement of undergraduates in the RTG is particularly noteworthy; over 80 such students carried out research under the auspices of the RTG during its first four years. ***