University of Vermont

College of Medicine

Department of Neurological Sciences

nishilab

 

Nishi Lab Research

As the nervous system develops, cell-cell interactions mediated by growth factors as well as synaptic interactions play an important role in survival and differentiation of specific cell types. The goal of our research is to attain a fundamental understanding of how these processes are regulated in the peripheral nervous system and how disruption of these mechanisms may lead to cancer or neurodegenerative disease.

One project in the lab that is funded by the National Institute of Drug Abuse is to understand how nicotinic signaling leads to programmed cell death during development and how this can be controlled. We have recently discovered 6 chicken genes that encode membrane-tethered molecules that fold into structures homologous to alpha-bungarotoxin, a molecule that blocks the activation of alpha-7 subunit containing nicotinic receptors. One of these molecules, the chicken ortholog of prostate stem cell antigen (chPSCA) is upregulated in the ciliary ganglion during the same time that half of the neurons are lost due to cell death. Misexpressing chPSCA rescues neurons from dying, suggesting that it may be an endogenous regulator of nicotinic receptor function. We are presently determining how such prototoxin molecules interact with alpha-7 containing receptors to protect cells from activity induced cell death.

A new pilot project in the lab funded by Alex’s Lemonade Stand is to determine how growth factor signaling through TrkB receptors may lead to the transformation of sympathoadrenal precursors into neuroblastoma. Using a mouse model of neuroblastoma cancer, the TH-MYCN mouse, we have discovered that key pathways of neurotrophin signaling are altered in tumors. We are using tissues from the embryos of these mice to determine how these signals are disrupted during development. We are also developing a new inducible mouse model of neuroblastoma.

 

Lab Personnel

Selected Publications

Simpson J, Keefe J and Nishi R. 2012. Differential Effects of Ret and TrkB on Axonal Branching and Survival of Parasympathetic Neurons Dev Neurobiol. In press. Abstract Full Text

Hruska M, Keefe J, Wert D, Tekinay AB, Hulce JJ, Ibañez-Tallon I, Nishi R. (2009). Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons. J Neurosci., 29(47):14847-54. PMID: 19940180. Abstract Full Text

Nishi R, Stubbusch J, Hulce JJ, Hruska M, Pappas A, Bravo MC, Huber LP, Bakondi B, Soltys J, Rohrer H. 2010. The cortistatin gene PSS2 rather than the somatostatin gene PSS1 is strongly expressed in developing avian autonomic neurons. J Comp Neurol. 518:839-850. Abstract

Hruska M. and Nishi R. (2007). Cell-Autonomous Inhibition of α7-Containing Nicotinic Acetylcholine Receptors Prevents Death of Parasympathetic Neurons during Development. J. Neurosci. 27(43):11501-11509. Abstract Full Text

Straub J., Sholler, G. and Nishi, R. (2007). Embryonic sympathoblasts transiently express TrkB in vivo and proliferate in response to brain-derived neurotrophic factor in vitro. BMC Dev Biol. 7:10-23. Abstract Full Text

Bunker, G. and Nishi, R. (2002). Developmental cell death in vivo: rescue of neurons independently of changes at target tissues. J. Comp. Neurol. 452:80-92. Abstract Full Text

Lee, V.L., Sechrist, J.W., Bronner-Fraser, M., and Nishi, R. (2002). Neuronal differentiation from post-mitotic precursors in the ciliary ganglion. Dev. Biol. 252:312-323. Abstract Full Text

Lee, V.L., Smiley, G.G. and Nishi, R. (2001). Cell death and neuronal replacement during formation of the avian ciliary ganglion. Devel. Biol. 233: 437-448. Abstract Full Text

Reiness, C.G., Seppa, M.J., Dion, D.M., Sweeney, S., Foster, D.N. and Nishi, R. (2001). Chick ciliary neurotrophic factor is secreted via a nonclassical pathway. Molec. Cell. Neurosci. 17: 931-944. Abstract

Darland, D.C. and Nishi, R. (1998). Activin and follistatin influence expression of somatostatin in the ciliary ganglion in vivo. Devel. Biol. 202: 293-303. Abstract Full Text

Finn, T.P., Kim, S. and Nishi, R. (1998). Overexpression of ciliary neurotrophic factor in vivo rescues chick ciliary ganglion neurons from cell death. J. Neurobiol. 34:283-293. Abstract Full Text

Last modified September 28 2012 08:30 AM