Ronald W. Oppenheim
Professor of Neurobiology and Anatomy Director, Neuroscience Program

B.A., 1962 Drake University
Ph.D., 1967 Washington University  

The development of a complex, multi-cellular animal from a single cell, the fertilized egg, is one of the most miraculous, intriguing and least understood events in biology. Shortly after fertilization the embryo begins to grow and develop rapidly by the gradual attainment of new cells, tissues, organs and functions. This progressive construction of new parts and functions is generally considered to be the hallmark of development. Yet beneath the surface of this biological construction process, seemingly insidious forces are at work which if unchecked could undermine the major goal of development. That is, while at one level of analysis constructive, progressive forces are gradually building the tissues and organs of the embryonic body, at other levels (cellular, molecular) non-pathological destructive and regressive events are occurring. Although these regressive events can take a number of different forms and may involve different cellular and molecular events, the most dramatic and devastating of these is cell death. 

In many different tissues and organs in the developing embryo, including the nervous system, massive numbers of differentiating cells degenerate and die. In some parts of the nervous system the cells that die may even outnumber those that survive. Because embryonic cell death is highly stereotyped in space and time and because it occurs to same extent in all individual members of a species, one can conclude that it is neither a random nor pathological process. By focusing on specific populations of neurons, we have been attempting to force the embryo to reveal its secrets regarding the mechanisms and significance of naturally occurring neuronal death. 

Previous studies have shown that the formation of early connections with targets and afferents plays an important role in regulating neuronal survival. The specific signals that mediate these target and afferent influences are of considerable interest. Recent studies suggest that synaptic transmission, post-synaptic activity, axonal branching and terminal contacts, and secreted neurotrophic molecules may all be used as signals to regulate the number of surviving neurons. We are attempting to understand the cellular and molecular events involved in each of these suspected regulatory processes. Attainment of this goal may help shed light on the reasons why neurons die pathologically later in life, as occurs in a variety of human neurodegenerative disorders, and may also aid in understanding the biological significance of this intriguing but still poorly understood phenomenon. 

Neuronal death is only one of many critical steps in the construction of a nervous system. The attainment of appropriate connections between neurons and their targets is another fundamental event that is of great interest to developmental neuroscientists. The emergence of adaptively appropriate behavioral patterns depends upon the formation of organized patterns of connectivity. We have been studying the formation of axonal pathways and synaptic connections by spinal cord neurons in the chick embryo that project within the central nervous system to spinal and brain targets. Our initial studies indicate that the pathways formed by the axons of these cells project unerringly in the appropriate locations and directions from the very onset of pathway formation. We are presently using in ovo and in vitro preparations for carrying out a variety of surgical, pharmacological and immunological perturbations to reveal the cellular, extracellular and molecular cues involved in pathway formation. Because the pathways involved here are used early in development for mediating pre- and post-natal behavior, these studies may also reveal important principles of early neurobehavioral development.

Recent Publications (selected):

Novak KD, Prevette D, Wang S, Gould TW, Oppenheim RW.:  Hepatocyte growth factor/scatter factor is a neurotrophic survival factor for lumbar but not for other somatic motoneurons in the chick embryo.  J. Neurosci. 20:326-37 (2000).

Gould TW, Burek MJ, Sosnowski JM, Prevette D, Oppenheim RW.:  The spatial-temporal gradient of naturally occurring motoneuron death reflects the time of prior exit from the cell cycle and position within the lateral motor column.  Dev. Biol. 216:611-21 (1999).

Gould TW, Burek MJ, Ishihara R, Lo AC, Prevette D, Oppenheim RW.:  Androgens rescue avian embryonic lumbar spinal motoneurons from injury-induced but not naturally occurring cell death.  J. Neurobiol. 41:585-95 (1999).

Oppenheim RW, Homma S, Marti E, Prevette D, Wang S, Yaginuma H, McMahon AP.:  Modulation of early but not later stages of programmed cell death in embryonic avian spinal cord by sonic hedgehog.  Mol. Cell. Neurosci. 13:348-61 (1999).

Li L, Prevette D, Oppenheim RW, Milligan CE.:  Involvement of specific caspases in motoneuron cell death in vivo and in vitro following trophic factor deprivation.  Mol. Cell. Neurosci. 12:157-67 (1998).