R. David Heathcote
Ph.D., Univ. of California, Berkeley 1981
Office: Lapham N411
Research InterestsOur interest in the development of the nervous system stems from the relatively simple idea that we can better understand how the nervous system works if we can figure out how it is put together. Toward this end, we are studying the patterns formed by newly generated neurons and the formation of synapses between motor neurons and their target muscles. Both of these problems are being studied in the nervous system of the frog, Xenopus laevis. We use a number of cellular and molecular techniques to study the mechanisms underlying these two problems. The techniques range from molecular biology including the formation of transgenic animals to embryonic dissection, intracellular injection, immunocytochemistry and many different types of light microscopy. Thus, our strategy is to use a multidisciplinary approach to try and understand how neurons become organized and form functional connections between cells.
We are studying the formation of patterns within the spinal cord. The organization of cells into patterns is a common developmental theme. The rules governing the formation of patterns could also indicate how the fate of a particular type of neuron is determined. We have identified a class of cells that contains dopamine and forms two distinctive columns within the floor plate region of the ventral spinal cord. The cells are not closely packed; rather other cells separate catecholaminergic neurons within each column. The arrangement is similar to the lateral inhibitory pattern seen in insect cuticle only it is in one dimension. The insect patterns are influenced by interactions between proteins made by neurogenic genes like Notch and Delta. Since homologs to these genes are expressed in the developing spinal cord, we would like to test their role in forming patterns of these differentiated neurons. We have also shown that a population of GABAergic cells form a similar pattern, but during a different period of development. We are interested in whether other populations of neurons form similar patterns and in the cellular and molecular interactions involved in the formation of spinal cord patterns. Ultimately we would like to know the rules involved in forming functional groups of cells.
We are also working on the molecular mechanisms involved in the formation of synapses at the developing neuromuscular junction. We are testing the "agrin hypothesis" which states that postsynaptic differentiation at the neuromuscular junction is induced by agrin, a protein secreted by the nerve terminal. To do this we are overexpressing genes like agrin and its receptors in developing embryos. These transgenic animals provide in vivo tests of the molecular mechanisms of synapse formation. The experiments will provide a better understanding of the molecular conversation between a neuron and its target during the formation of functional connections.
- Binor, E. and Heathcote, R.D. (2005) Activated Notch disrupts the initial patterning of dopaminergic spinal cord neurons. Dev. Neurosci. 27, 306-312. Abstract
- Moghadam, K.S., Chen, A and Heathcote, R.D. (2003) Establishment of a ventral cell fate in the spinal cord. Dev. Dyn. 227, 552-562. Abstract
- Binor, E., and Heathcote, R.D. (2001) Development of GABA-immunoreactive neuron patterning in the spinal cord. J. Comp. Neurol. 438, 1-11.Abstract
- Heathcote, R.D., Ekman, J.M., Campbell, K.P., and Godfrey, E.W. (2000) Dystroglycan overexpression in vivo alters acetylcholine receptor aggregation at the neuromuscular junction.Devl. Biol. 227, 595-605.Abstract
- Godfrey, E.W., Roe, J., and Heathcote, R.D. (2000) Agrin fragments differentially induce ectopic aggregation of acetylcholine receptors in myotomal muscles of Xenopus embryos. J. Neurobiol. 44, 436-445.Abstract
- Chen, A., Ekman, J., and Heathcote, R.D. (1999) Reduction in cell size during development of the spinal cord. J. Comp. Neurol.409, 592-602.Abstract
- Godfrey, E.W., Roe, J., and Heathcote, R.D. (1999) Overexpression of agrin isoforms in Xenopus embryos alters the distribution of synaptic acetylcholine receptors during development of the neuromuscular junction. Devl. Biol. 205, 22-32. Abstract
- Heathcote, R.D. (1997) Origin and morphogenesis of neurons in the frog cardiac ganglion. Kaohsiung J. Med. Sci. 13, 36-41. Abstract
- Heathcote, R.D. (1996) Spatial and temporal shifts in the regulation of neurogenesis in a peripheral ganglion. J. Comp. Neurol. 375, 457-466. Abstract
- Heathcote, R.D. and Chen, A. (1994) Morphogenesis of catecholaminergic interneurons in the frog spinal cord. J. Comp. Neurol., 342, 57-68. Abstract
- Heathcote, R.D. and Chen, A. (1993) A nonrandom interneuronal pattern in the developing frog spinal cord. J. Comp. Neurol. 328, 437-448. Abstract