Department of
Psychological and Brain Sciences

• Molecular neuroscience

• Neuregulen-ErbB signaling in the nervous system
• BAC-based transgenic mouse models of neural function

Our lab uses molecular biological approaches to study the nervous system. One major area of interest is the role of neuregulin-ErbB signaling in neuronal and glial function. The neuregulins are a collection of polypeptides that activate a family of transmembrane signaling molecules, the receptor tyrosine kinases known as the ErbBs. There is considerable interest in this signaling pathway as the neuregulin-1 gene has been implicated as a risk factor for the neuropsychiatric disorder schizophrenia. The neuregulin receptor ErbB4 is expressed by multiple populations of migrating neuronal precursors in the developing brain and our studies have helped to show that alterations in ErbB4 function may influence the final placement of these cells. These changes may lead to alterations in brain circuitry, a finding that provides one potential mechanism by which neuregulin-ErbB signaling may contribute to an increased risk for schizophrenia. One of the current lab interests is to understand the precise molecular role that ErbB4 plays within the migrating neuronal precursors.

A second focus of the lab has been the development of transgenic mouse tools useful for studying the nervous system. Our goal has been to produce lines of mice that permit both temporal and spatial regulation of gene expression in specific subsets of cells in the brain. Using a BAC-based approach, we have successfully produced lines of transgenic mice that permit regulated expression in cholinergic neurons and are developing similar lines for use in dopaminergic neurons and in the medium spiny neurons in the striatum. The overall goal is to use these mice to study the neurodegenerative process, and we anticipate that these lines will facilitate efforts to gain an improved understanding of Alzheimer's, Parkinson's and Huntington's diseases.

Chen, Y.-J., Zhang, M., Yin, D.-M., Wen, L., Ting, A., Wang, P., Lu, Y.-S., Zhu, X.-H., Li, S.-J., Wu, C.-Y., Wang, X.-M., Lai, C., Xiong, W.-C.-, Mei, L., and Gao, T.-M. (2010) ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation. Proc Natl Acad Sci (USA) 107:21818-21823.

Brinkmann, B.G., Agarwal, A., Sereda, M.W., Garratt, A.N., Muller, T., Wende, H., Stassart, R.M., Nawaz, S., Humml, C., Velanac, V., Radyushkin, K., Goebbels, S., Fischer, T.M., Franklin, R. J., Lai, C., Ehrenreich, H., Birchmeier, C., Schwab, M.H., and Nave, K.-A. (2008) Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. Neuron, 59: 581-595.

Prieto, A.L., O’Dell, S., Varnum, B., and Lai, C. (2007) Localization and signaling of the receptor protein tyrosine kinase Tyro-3 in cortical and hippocampal neurons. Neuroscience, 150:319-334.

Ghashghaei, H.T., Weber, J.L., Pevny, L., Schmid, R., Schwab, M.H., Lloyd, K.C., Eisenstat, D.D., Lai, C., and Anton E. S. (2006). The role of neuregulin-erbB4 interactions on the proliferation and organization of cells in the adult subventricular zone. Proc Natl Acad Sci (USA), 103:1930-1935.

Michailov, G.V., Sereda, M.W., Brinkmann, B.G., Fischer, T.M., Haug, B., Birchmeier, C., Role, L., Lai, C., Schwab, M.H. and Nave, K.-A. (2004) Axonal neuregulin-1 regulates myelin sheath thickness. Science 304, 700-3.

Anton, E.S., Ghashghaei, H.T., Weber, J.L., McCann, C., Fischer, T.M., Cheung, I.D., Gassmann, M., Messing, A., Klein, R., Schwab, M.H., Lloyd, K.C.K. and Lai, C. (2004) Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain. Nat. Neurosci. 7, 1319-1328.

Carraway III, K. L. , Weber, J. L., Unger, M. J., Ledesma, J., Yu, N., Gassmann, M. and Lai, C. (1997). Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. Nature 387, 512-516.