Yi Rao

Yi Rao , Ph.D.*

Associate Professor

Anatomy & Neurobiology



We are interested in cellular and molecular mechanisms underlying axon guidance and neuronal migration in vertebrates. We study cell-cell interactions that control neuronal migration, identify extracellular molecular cues that guide the direction of neuronal migration and investigate intracellular signal transduction mechanisms that mediate cellular responses to extracellular cues.



In the mammalian cerebellum, we have discovered cellular interactions that determine the timing and direction of the migration of cells from the external germinal layer (EGL) to the internal granule layer (IGL). An attractive signal has been found to play a role in anchoring the EGL cells in the embryonic cerebellum, whereas a repulsive is responsible for directing the postnatal EGL to migrate towards the IGL. Because EGL migration is a model for cortical migration, these findings suggest that similar mechanisms may function in neocortical development.



In the olfactory system, the interneurons in the olfactory bulb are derived from cells migrating from the anterior subventricular zone (SVZa) in the forebrain. The secreted protein Slit has been shown to be a repellent that may be involved in directing the SVZa cells towards to the olfactory bulb. It would be interesting to know whether other extracellular cues function together with Slit to direct the SVZa cells.



We have started to investigate the signal transduction pathway mediating cellular responses to guidance cues. Slit protein binds to the transmembrane receptor Roundabout (Robo). One component downstream of Robo is a GTPase Activation Protein (GAP) that regulates the activity of small GTPases of the Rho subfamily. Functional studies indicate that the Rho GTPases are important for Slit-Robo signaling, providing a basis to further understand the signal transduction pathways for neuronal guidance cues.



• neural development, neuronal migration, axon guidance, molecular signals, signal transduction



10 word: Molecular signaling in axon guidance and neuronal migration



Wu W, Wong K, Jiang ZH, et al. Guidance of neuronal migration in the olfactory system by the secreted protein Slit. Nature 1999 400:331-336.



Zhu Y, Li HS, Zhou L, et al. Cellular and molecular guidance of GABAergic neuronal migration from an extra-cortical origin to the neocortex. Neuron 1999 23:31-43.



Li HS, Chen JH, Wu W, et al. Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons. Cell 1999 96:807-818.



Chen J, Wen L, Dupuis S, et al. The N-terminal leucine rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons. J. Neurosci. 2001 21: 1548-1556.



Wu JY, Feng L, Park H-T, et al. The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature 2001, 410:948-952.



Wong, K., Ren, X.-R., Huang, Y.-Z., Xie, Y., Liu, G., Saito, H., Tang, H., Wen, L., Brady-Kalnay, S. M., Mei, L., Wu, J. Y., Xiong, W.-C., and Rao, Y. Signal transduction in neuronal migration: Roles of GTPase activating proteins and the small GTPase Cdc42 in the slit-robo Pathway. Cell, 2001, 107:209-221





*=member, Division of Biology & Biomedical Sciences



927 McDonnell Sciences Bldg.

Phone: 314-362-9388

Campus Box: 8108

Fax: 314-362-3446

raoyi@thalamus.wustl.edu

http://thalamus.wustl.edu/raolab/