Faculty Research Page

Gian Garriga
Professor of Genetics, Genomics and Development*
*And Affiliate, Division of Neurobiology
Research Interests
We are studying how asymmetric cell division, cell migration and axonal pathfinding contribute to the final form and connectivity of the Caenorhabditis elegans nervous system.
Current Projects
Asymmetric neuroblast
divisions. Nervous systems contain
many different cell types. 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 specific
neuroblasts that divide asymmetrically to generate an apoptotic cell and a
neuron or neural precursor. 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 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 molecules
that interact to orient neuronal polarity and guide migrating cells and growth
cones. VAB-8, a novel kinesin-like protein orients polarity of neurons toward
the posterior and promotes directed cell and growth cone migrations toward the
posterior of the animal. VAB-8, 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 antagonistically
to VAB-8, orienting the polarity of neurons toward the anterior and guiding 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 how Frizzled receptors transduce their signals in neuronal polarity
and axon guidance is unclear. We are using genetic approaches to define these
intracellular signaling pathways.
Selected Publications
The Flamingo orthologue FMI-1 controls pioneer-dependent navigation of
follower axons in C. elegans.
[A. Steimel, L. Wong, E.H. Najarro, B.D. Ackley, G. Garriga and H. Hutter.
(2010) Development In press.]
The role of the C. elegans
Mena/VASP homolog UNC-34 in neuronal polarity and motility. [T. Fleming, S.–C.
Chien, P.J. Vanderzalm, M. Dell, M.K. Gavin, W.C. Forrester and G. Garriga
(2010) Developmental Biology 344:
94-106.]
C. elegans CARMIL negatively regulates UNC-73/Trio function
during neuronal development. [P.J. Vanderzalm, A. Pandey, M.E. Hurwitz, L.
Bloom, H.R. Horvitz and Garriga, G. (2009) Development 136,
1201-1210.]
Asymmetric cell division,
aggresomes and apoptosis. [A. Singhvi 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. [A.
Singhvi, 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]
Last Updated 2010-08-06