Dr. Ruth Seigel

Research Interests:

Our research seeks to understand events that regulate the postnatal differentiation of the rat cerebellum. Unlike most of the brain, this region differentiates extensively during the first three weeks of life. During this time, cells at the cerebellar cortex divide and then migrate inward to form the mature cerebellum.

A major focus of our studies is the onset and expression of the GABA A receptor during cerebellar development. This multifunctional receptor mediates the actions of ?-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, as well as many clinically important compounds (e.g., Librium and Phenobarbital). The receptor is composed of five subunits, most of which are encoded by gene families. Our studies on cerebellar granule neurons in vivo and in culture have provided insights into receptor gene expression and assembly during postnatal ontogeny. Our findings demonstrate that the eight receptor subunits expressed by cerebellar granule neurons are differentially regulated. Furthermore, subunit polypeptide expression is controlled both at the level of the mRNA and during assembly into cell surface receptors. While the d subunit transcript is induced by depolarization-dependent Ca 2+ influxes, other subunit mRNAs increase in response to extrinsic developmental cues. Most notably, expression of the ß2 subunit, which confers sensitivity to GABA, is induced by neuregulin, a growth and differentiation factor. The effects of neuregulin on granule neuron development and the mechanism of its action is a major focus of current research.

Phone: (216) 368-5554
Fax: 216-368-1300
E-mail: ruth.siegel@case.edu
W309C Wood Building

http://pharmacology.case.edu/department/faculty/primary/Pages%5Csiegel.aspx