Faculty and Research
Faculty by Name
Gian Garriga
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Gian Garriga
Professor of Genetics, Genomics and Development*
*And Affiliate, Division of Neurobiology
Research Interests
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To understand how nervous systems develop, we are studying how asymmetric cell division, neuronal polarity, cell migration and axonal pathfinding contribute to the final form and connectivity of the Caenorhabditis elegans nervous system.
Current Projects
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Asymmetric neuroblast divisions. Nervous systems contain many different types of neurons. One way to generate this diversity is for neuroblasts to divide asymmetrically, producing daughter cells that adopt distinct fates. We have identified several proteins that function in several C. elegans neuroblasts, ensuring that they divide asymmetrically to generate apoptotic cells and neural precursors. These proteins regulate the position of the neuroblast spindle and the distribution of developmental potential to daughter cells. Our current focus is to understand how Frizzleds, cell surface receptors for Wnt glycoproteins, orient these divisions and how membrane trafficking events regulate the function of Frizzled receptors.
Neuronal polarity and migrations. When neurons are born, they often migrate to the new positions where they differentiate. These migrations shape nervous system structure. Once in their final positions, neurons polarize and extend an axonal growth cone that navigates to reach its synaptic targets. The establishment of polarity and the ability of axons to find their targets are essential steps in establishing the connections between neurons that underlies behavior. We are studying molecules that orient the polarity and guide the migrations of these neurons and their growth cones along the C. elegans anterior/posterior (A/P) axis.
Polarity and guidance along the A/P axis appears to be regulated by the activity of several cues . VAB-8L, a novel kinesin-like protein, orients neuronal polarity and promotes directed cell and growth cone migrations toward the posterior of the animal. VAB-8L, acting with the conserved Rac exchange factor UNC-73/Trio, increases levels of the receptors that promote posterior polarity and guidance, We are particularly interested in defining the mechanism of how VAB-8L and UNC-73 control the levels and distributions of these receptors.
Wnts, secreted glycoproteins that function in several different developmental processes, act as cues to orient neuronal polarity and guide the anterior migrations of C. elegans cells and growth cones. The effects of the Wnts are mediated by Frizzled receptors. Wnts and Frizzleds also act to guide growth cones along the mammalian spinal cord, but little is know about how Frizzled receptors transduce their signals in neuronal polarity and axon guidance. We are particularly interested in defining these intracellular signaling pathways and studying molecules that shape Wnt gradients.
Axon fasciculation. In C. elegans, growth cones extend along specific axons to generate highly ordered nerve bundles or fascicles. We have recently begun a project to develop methods to detect these specific axon-axon interactions and to perturb specific interactions using RNA interference techniques. Our goal is to understand how axon fascicles develop.
Selected Publications
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C. elegans CARMIL negatively regulates UNC-73/Trio function during neuronal development. [Vanderzalm, P.J., A. Pandey, M.E. Hurwitz, L. Bloom, H.R. Horvitz and Garriga, G. (2009) Development 136, 1201-1210.]
Asymmetric cell division, aggresomes and apoptosis. [Singhvi, A. and G. Garriga (2009) Trends in Cell Biology 19, 1-7]
The T-box gene tbx-2 and the homeobox gene egl-5 specify neural fate in the HSN/PHB lineage. [Singhvi, A., C.A. Frank, and G. Garriga (2008) Genetics 179, 887-898.]
C. elegans AP-2 and retromer control Wnt signaling by regulating MIG-14/Wntless. [C. L. Pan, P. D. Baum, M. Gu., E. M. Jorgensen, S.G. Clark and G. Garriga (2008) Developmental Cell 14, 132-139.]
C. elegans VAB-8L and UNC-73/Trio regulate the SAX-3/Robo receptor to direct cells and growth cones posteriorly. [N. Watari-Goshima, K. Ogura, F. W. Wolf, Y. Goshima and G. Garriga (2007) Nature Neuroscience 10, 169-176.]
The C. elegans MELK ortholog PIG-1 kinase regulates cell size asymmetry and daughter cell fate in asymmetric neuroblast divisions. [S. Cordes, C. A. Frank and G. Garriga (2006) Development 133, 2747-2756]
Multiple Wnt homologs regulate anteriorly directed cell and growth cone migrations in C. elegans. [C. L. Pan, J. Endres-Howell, S. Clark, M. Hilliard, S. Cordes, C. I. Bargmann, and G. Garriga (2006) Developmental Cell 10, 367-377]
Sensitized genetic backgrounds reveal a role for C. elegans FGF EGL-17 as a repellent for migrating CAN neurons. [T. Fleming, F. W. Wolf, and G. Garriga (2005) Development 132, 4857-4867]
C. elegans HAM-1 positions the cleavage plane and regulates apoptosis in asymmetric cell divisions. [C. A. Frank, N. C. Hawkins, C. Guenther, H. R. Horvitz and G. Garriga (2005) Developmental Biology 284, 301-310]The C. elegans Frizzled MOM-5 regulates the distribution of DSH-2 to control asymmetric cell division. [N. Hawkins, G. C. Ellis, B. A. Bowerman and G. Garriga (2005) Developmental Biology 284, 246-259]
The C. elegans Ror RTK CAM-1 inhibits EGL-20/Wnt signaling in cell migration. [W. C. Forrester, C. Kim and G. Garriga (2004) Genetics 168, 151-162]
The conserved kinase UNC-51 acts with VAB-8 and UNC-14 to regulate posteriorly directed axon outgrowth in C. elegans. [T. Lai and G. Garriga (2004) Development 131, 5991-6000]
Last Updated 2009-06-23