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Joseph J. LoTurco neocortical development and function The research goals in my laboratory are to i) define the cellular and molecular signals that promote and regulate the generation and migration of neurons within the neocortex, ii) understand why certain disruptions in normal neocortical development cause epilepsy, and learning disorders, and iii) understand how production of new neurons in the mature brain may be used to repair damaged neuronal circuits. Our experiments make use of multiple approaches and technologies including retrovirus-mediated gene-transfer, in utero gene transfer, siRNA, confocal microscopy, patch-clamp electrophysiology and immunocytochemistry. With this combination of approaches we strive to unravel how the most sophisticated computing device in nature is constructed, how its malformation leads to neurological disease, and how we might repair it in the future through triggered neuronal replacement. I completed my Ph.D. in Neurosciences at Stanford University in 1991, where I used patch-clamp techniques to define the neurotransmitter receptors and ion channels that mediate interactions in the earliest phases of neocortical development. I then went to the Department of Genetics at Harvard Medical School for my post-doctoral studies, where I continued work on defining signaling systems that promote the differentiation of neuronal progenitors and gained training in molecular genetic technologies. I have had my own lab at the University of Connecticut since 1994. Our recent work has focused on determining how the neurons that populate the mature neocortex are generated and migrate to form functional layers. We have focused our efforts on a set of genes that when mutated in humans or rodents lead to malformations that clearly indicate their critical role in either neuronal production or migration. Two genes of particular interest are Citron-kinase, essential to neurogenic cell division, and doublecortin, essential to radial migration. We are now identifying the specific cellular functions controlled by these proteins, and identifying the proteins that interact with them. 23
Selected Publications Bai, J., et al. (2003). RNAi reveals doublecortin is required for radial migration in rat neocortex. Nat Neurosci. 6(12): 1277-83. Meng, H., et al. (2005). DCDC2 is associated with reading disability and modulates neuronal development in the brain. Proc Natl Acad Sci USA 102(47): 17053-8. Ramos, R.L., J. Bai, and J.J. LoTurco. (2006). Heterotopia Formation in Rat but Not Mouse Neocortex after RNA Interference Knockdown of DCX. Cereb Cortex. Paracchini, S., et al. (2006). The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration. Hum Mol Genet, 2006. 15(10): 1659-66. LoTurco, J.J. and J. Bai. (2006). The multipolar mode and neuronal migration disorders. Trends in Neuroscience 27(7): 407. Ackman, J., R. L. Ramos, M. R. Sarkisian, and J. J. LoTurco. (2007). Citron Kinase is Required for Postnatal Neurogenesis in the Hippocampus. Dev Neurosci. 29(1-2): 113-23. Galaburda, A. M., J. J. LoTurco, F. Ramus, R. H. Fitch, G. D. Rosen. (2006). From genes to behavior in developmental dyslexia. Nat Neurosci. 9(10):1213-7. Ackman, J. B., F. Siddiqi, R. S. Walikonis, LoTurco J. J. (2006). Fusion of microglia with pyramidal neurons after retroviral infection. J Neurosci. 26(44):11413-22. Wang, Y., M. Paramasivam, A. Thomas, J. Bai, N. Kaminen- Ahola, J. Kere, J. Voskuil, G. D. Rosen, A. M. Galaburda, J. J. LoTurco. (2006). DYX1C1 functions in neuronal migration in developing neocortex. Neuroscience 143(2):515-22. Paramasivam, M., Y. J. Chang, and J. J. LoTurco. (2007). ASPM and Citron Kinase Co-Localize to the Midbody Ring During Cytokinesis. Cell Cycle 6(13). Bai J., R. L. Ramos, M. Paramasivam, F. Siddiqi, J. B. Ackman, J. J. LoTurco. (2008). The role of DCX and LIS1 in migration through the lateral cortical stream of developing forebrain. Dev Neurosci. 30(1-3):144-56. Manent, J. B., Y. Wang, Y. J. Chang, M. Parmasivam and J. J. LoTurco. (2009). Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder. Nature Medicine 15 (1) 84-90. Loturco, J. J., J. B. Manent, F. Siddiqi. (2009). New and Improved Tools for In Utero Electroporation Studies of Developing Cerebral Cortex. Cerebral Cortex.
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Page 9 and 10: Selected Publications Cantino, M.E.
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