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Neuroscience Graduate Program at UCSF
Wnt Signaling in Development and Function of the Mammalian Brain
Wnt Signaling in Brain Physiology
Intercellular communication is critical for the development and function of all multicellular organisms. Our laboratory is investigating the role of intercellular communication in the mammalian brain. Our focus is on a type of intercellular communication known as Wnt signaling, which has been implicated in neuropsychiatric illness.
Wnts are an ancient family of secreted glycoproteins conserved across animal species. Transmembrane Wnt receptor complexes transmit information from the extracellular space to the cytoplasm and nucleus through multiple protein cascades. The type of signaling cascade activated in target cells downstream of Wnts and their receptors is modulated by intracellular scaffold proteins. Though their cell biology is not well understood, scaffold proteins are thought to mobilize other components to the signaling complex depending on their levels and subcellular localization. We have focused our attention on Wnt signal scaffold proteins and how they work, particularly during neuronal development and physiology.
The major experimental paradigm in our lab is the neurodevelopmental and behavioral characterization of genetically engineered mice. A current major thrust is mice with engineered defects in the Dact (Dpr/Frd) gene family. This work is complemented by assays of Wnt signaling and cellular phenotypes in immortalized and primary tissue culture. Another objective is the identification of proteins that functionally interact in the developing and mature brain with these scaffold proteins. Our goal in conducting this work is to gain insight into the molecular basis for human behavior, neuropsychiatric illness, and its treatments.
1. Forebrain phenotypic analysis in Dact1 mutant mice (developmental neuroanatomy/histology)
2. Histological correlates of potential behavioral defects in combination mutants (neuroanatomy/histology + minimal behavioral studies)
3. Role of Dact proteins in Wnt/ß-catenin signaling (biochemistry, siRNA techniques, cell culture)
4. Dact protein-protein interactions (molecular biology, biochemistry, cell culture)
Ben Cheyette
PI
bc@lppi.ucsf.edu
Saul Kivimae
Post-doctoral fellow
skivimae@lppi.ucsf.edu
Dan Fisher
Graduate Student Wash. U., Neuroscience/MSTP
danielf@lppi.ucsf.edu
Rowena Suriben
Graduate Student
UCSF Tetrad
rowenasuriben@hotmail.com
Nathan Okerlund
Graduate Student
UCSF Tetrad
nathan.okerlund@ucsf.edu
Suriben, R, Fisher, DA, Cheyette, BNR (2006). Dact1 Presomitic Mesoderm Expression Oscillates in Phase with Axin2 in the Somitogenesis Clock of Mice. Dev Dyn 235.
Fisher DA, Kivimäe S, Hoshino J, Suriben R, Martin P-M, Baxter N, Cheyette BNR (2006). Three Dact Gene Family Members are Expressed During Embryonic Development and in the Adult Brains of Mice. Dev Dyn 235: 2620-2630.
Cheyette BNR (2004). Ryk, another Heretical Wnt Receptor Defies the Canon. Science STKE 263, pe54.
Cheyette, B.N.R., Waxman, J.S., Miller, J.R., Takemaru, K.I., Sheldahl, L.C., Khlebtsova, N., Fox, E.P., Earnest, T., and Moon, R.T. (2002). Dapper, a Dishevelled-Associated Antagonist of ß-catenin and JNK Signaling, is Required for Notochord Formation. Developmental Cell 2, 449-461.
Benjamin Cheyette, MD/Ph.D.
Phone
415-476-7826
Physical Address
Rock Hall
1550 4th Street
RH-284D
Mailing Address
Cheyette Lab
UCSF MC 2611
Rock Hall Room 284D
1550 4th St
San Francisco, CA 94158-2324
For Internal Campus Mail
Box 2611
Other Websites
Biomedical Sciences Graduate Program
Pharmaceutical Sciences & Pharmacogenomics