Jane L. Witten Associate Professor B.A., Wesleyan Univ. 1974 Ph.D., Univ. of Chicago 1984 Post-doctoral Fellow Univ. of Washington 1986-90 Univ. of Arizona 1990-92	Office:Lapham N408 Phone: 414-229-4993 FAX: 414-229-3926 Email: jlw@uwm.edu Electronic Reserve Materials:
Cellular and Molecular Neuroscience

Research Interests

Animals live in a constantly changing environment. Survival demands that nervous systems must be flexible to accommodate to these changes. My research interests are to elucidate the cellular and molecular mechanisms that produce this flexibility or plasticity. We are focusing on how hormones, modulatory neurotransmitters (neuropeptides), and ion channels interact to contribute to nervous system development, flexibility and function. We are taking a multi-disciplinary approach using physiological, biochemical, immunochemical, and molecular techniques to address these questions. The model system that we use for our studies is metamorphosis of the tobacco hornworm, Manduca sexta. The nervous system of this animal contains a relatively small number of neurons, most of which can be studied as identified individuals. Metamorphosis results in a dramatic reorganization of the moth's nervous system facilitating our search for mechanisms underlying neuronal and behavioral plasticity. We have shown that a family of neuropeptides, FLRFamides, are differentially expressed and developmentally regulated. This family of peptide neurotransmitters is present in larval motoneurons but levels decline during metamorphosis under the influence of steroid hormones. They are absent in adult motoneurons, even though the motoneurons and muscles persist. In contrast, these peptides are expressed in neurosecretory cells throughout the metamorphic transitions. Thus, the same hormonal signals have distinct effects on the gene expression of FLRFamide peptides in different neurons. Our biochemical studies suggest the neurosecretory cells release these neuropeptides at each molt and we propose they modulate muscles to coordinate molting behavior. Our recent molecular studies suggest that multiple genes encode the Manduca FLRFamide peptide family. Current research is focused on investigating the physiological actions of this neuropeptide family on skeletal and visceral muscles, elucidating the cellular and molecular mechanisms of neuropeptide action on muscle, and isolating the genes encoding other members of this family. Our investigation of how modulation of ion channels may contribute to neuronal plasticity is focusing on voltage-gated potassium ion channel families. Defects in the normal development or functioning of these ion channels can lead to disruption of neuronal signaling and then to neurological and neuromuscular diseases. We have recently cloned and molecularly characterized the Manduca eag and Manduca slowpoke homologs and immunochemically characterized Manduca Shaker-like proteins. Currently, we are studying their cellular distribution, developmental expression, and functions.

Selected Publications

Keyser MR and Witten JL (2005) Calcium-Activated Potassium Channel of the Tobacco Hornworm Manduca sexta: Molecular Characterization and Expression Analysis. J. Exp. Biol. 208: 4167-4179. Keyser MR, Anson BD, Titus SA, Ganetzky B, and Witten JL (2003) Molecular Characterization, Functional Expression, and Developmental Profile of an Ether à go-go K+ Channel in the Tobacco Hornworm Manduca sexta. J. Neurobiol 55: 73-84. Lu D, Lee K-Y, Horodyski FM, and Witten JL (2002) Molecular characterization and cell-specific expression of a Manduca sexta FLRFamide gene. J. Comp. Neurol. 446: 377-396. Miao, YS, Waters, EM, and Witten, JL (1998) Developmental and regional-specific expression of FLRFamide peptides in the tobacco hornworm, Manduca sexta, suggest functions in ecdysis. J. Neurobiol. 37: 468-484. Witten JL and Truman JW (1998) The distribution of GABAergic lineages in insects suggest lineage homology. J. Comp. Neurol. 398: 515-528. Witten JL and Truman JW (1996) Steroid regulation of neuropeptide plasticity in motoneurons during metamorphosis of an insect. J. Neurobiology 29: 99-114. Kingan TG, Shabanowitz J, Hunt DF and Witten, JL (1996) Characterization of two myotropic neuropeptides in the FMRFamide family from the segmental ganglia of the moth Manduca sexta: Candidate neurohormones and neuromodulators. J. Exp. Biol. 199: 1095-1104. Witten JL and Truman JW (1996) Developmental plasticity of neuropeptide expression in motoneurons of the moth, Manduca Sexta: Steroid hormone regulation. J. Neurobiology 29:99-114. 1996. Pfluger HJ, Witten JL, and Levine RB (1993) Fate of abdominal ventral unpaired median cells during metamorphosis of the hawkmoth, Manduca sexta. J. Comp. Neurol. 355: 508-522. Witten JL and Truman JW (1991a) The regulation of transmitter expression in postembryonic lineages in the moth, Manduca sexta. I: Transmitter identification and developmental acquisition of expression. J. Neurosci. 11: 1980-89. Witten JL and Truman JW (1991b) The regulation of transmitter expression in postembryonic lineages in the moth, Manduca sexta. II: Role of cell lineage and birth order. J. Neurosci. 11: 1990-97. Witten JL and O'Shea M (1985) Peptidergic innervation of insect skeletal muscle: Immunochemical observations. J. Comp. Neurol. 242:93-101.