My research is focused on understanding molecular mechanisms controlling peripheral nerve development with emphasis on regulation of growth and differentiation of Schwann cells into myelin-forming cells. Major pathways examined are transduction of extracellular matrix signals through integrin receptors and neuregulin signalling through erbB2/erbB3 receptors. The integration of these pathways with those regulating cytoskeleton organization through the rho family of GTPases is under study.
We have found that schwannomin/merlin the product of the Neurofibromatosis type 2 gene is a direct binding protein with paxillin, an integrator of extracellular matrix and growth factor signalling with changes in the actin cytoskeleton. The interacting domain in schwannomin is mutated in humans with NF2 mutations and leads to tumor formation.
The studies are conducted using primary Schwann cells in isolation or together with sensory neurons to study development of myelin in vitrol. These studies are funded by a long-standing grant from NIH/NINDS and have application for the understanding of various demyelinating diseases as well as abnormal growth of Schwann cells.
Recent Publications - Fernandez-Valle, C, Tang, Y., Ricard, J., Ruano-Rodenas, A., Hackler, E., Taylor, A.,Biggerstaff, J., Iacovelli, J. 2002. Paxillin binds schwannomin and regulates its density dependent localization and effect on cell morphology. (2002) Nature Genetics 31: 354-62.
- Taylor, A., and Fernandez-Valle, C. (2003) RhoGTPase is not required for formation of a ß1 Integrin Multi-Molecular Complex in Schwann Cells. GLIA 41: 94-104.
- Thaxton, C., Lopera, J., Bott, M., Baldwin, M.E., Kalidas, P., Fernandez-Valle, C. Phosphorylation of the NF2 tumor supressor in Schwann cells is mediated by Cdc42-Pak and requires paxillin binding. Mol. Cell. NeuroSci. 34(2): 231-42.
- Iacovelli J, Lopera J, Bott M, Baldwin ME, Khaled A, Uddin N, Fernandez-Valle C (2007). Serum and forskolin cooperate to promote G1 progression in Schwann cells by differentially regulating cyclin D1, cyclin E1, and p27Kip expression. Glia 55(16): 1638-47.
- Thaxton C, Lopera J, Bott M, Fernandez-Valle C (2007) Neuregulin and laminin stimulate phosphorylation of the NF2 tumor supressor in Schwann cells by distinct protein kinase A and p21-activated kinase-dependent pathways. Oncogene. doi: 10.1038/sj.onc.1210923.
