Neuroscience Graduate Program

Neuroscience Graduate Program at UCSF

Faculty - Benjamin Cheyette, MD/Ph.D.

Signaling Scaffold Proteins in Development and Major Psychiatric Disorders

Research Description

We are investigating intracellular proteins that regulate signaling pathways and cytoskeletal dynamics in neurons. We seek to understand how these proteins operate both in the developing embryo and in the brain. Our embryonic studies are particularly relevant to birth defects, whereas our brain studies are relevant to the biology of major mental illnesses such as autism, schizophrenia, and bipolar disorder. We have found that these approaches are highly complementary: our discoveries in the embryo inform our investigations in the brain and vice-versa. For example, recent work has uncovered critical dual roles for one protein during gastrulation (embryonic tissue morphogenesis) at the primitive streak, as well as later in the formation and maintenance of dendrites and synapses. We are also interested in discovering new links between such molecules and susceptibility to major mental illnesses by harnessing next-generation (massively parallel) sequencing technologies. The experimental tools we primarily use are recombinant DNA technology, mammalian tissue culture, and neurodevelopmental and behavioral assays in gene-targeted and transgenic strains of laboratory mice.

Current Projects

1. Characterization of neuron and brain phenotypes resulting from novel targeted mutations in mice

2. Identification of mental-illness-associated gene variants in human populations and their effects on neuron morphology, function, and on behavior in mouse models

3. Elucidation of novel biochemical pathways operating in neurons involving the genes/proteins in #1 and #2

4. Mechanistic investigations of embryological phenotypes resulting from the same novel targeted mutations in mice, when operating earlier and elsewhere in development

Lab Members

Annie Arguello, Graduate Student
Saul Kivimae, Postdoctoral Fellow
Pierre-Marie Martin, Postdoctoral Fellow
Petros Minasi, Lab Manager
Kimberly Mulligan, Postdoctoral Fellow
Robert Stanley, Graduate Student
Xiao Yong Yang, Postdoctoral Fellow
Susan Yu, Administrative Assistant

Selected Publications

Okerlund ND, Cheyette BNR (2011). Synaptic Wnt Signaling – A Contributor to Major Psychiatric Disorders? J. Neurodev Dis, 3(2):162-74. PMCID: PMC3180925

Kivimäe S, Martin P-M, Kapfhamer D, Ruan Y, Heberlein U, Rubenstein JLR, Cheyette BNR (2011). Abnormal behavior in mice mutant for the Disc1 binding partner, Dixdc1. Translational Psychiatry, 1, e43 [Epub].

Kivimäe S, Yang XY, Cheyette BNR (2011) All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl2, Dvl, and serine threonine kinases. BMC Biochemistry, 12(1):33 PMCID: PMC3141656

Okerlund ND, Kivimäe S, Tong CK, Peng I-F, Ullian EM, Cheyette BNR (2010). Dact1 is a postsynaptic protein required for dendrite, spine, and excitatory synapse development in the mouse forebrain. J. Neurosci, 30(12):4362-8. PMCID: PMC2848693.

Suriben R, Kivimäe S, Fisher DA, Moon RT, Cheyette, BNR. Posterior Malformations in Dact1 mutant mice arise through misregulated Vangl2 at the Primitive Streak. Nat Genet, http://dx.doi.org/10.1038/ng.435

Louie S, Yang XY, Conrad WH, Muster J, Angers S, Moon RT, Cheyette BNR. Modulation of the ß-catenin Signaling Pathway by the Dishevelled-associated Protein Hipk1. PLoS ONE, 4: e4310, 2009.

Cheyette, BNR, Cheyette, SNR, Cusmano-Ozog, K, Enns, GM. Dopa-responsive dystonia presenting as delayed and awkward gait. Pediatric Neurology, 38: 273-275, 2008.

Jiang, T, Tan, J, Li, J, Kivimäe, S, Zhuang, L, Lee, PY, Chan, MTW, Liu, ET, Cheyette, BNR, Yu, Q. DACT3 is a Key Epigenetic Regulator of Wnt/ß-catenin Signaling in Colorectal Cancer and is a Therapeutic Target of Histone Modifications. Cancer Cell, 13: 529-541, 2008.

Suriben, R., Fisher, DA, Cheyette, BNR. Dact1 Presomitic Mesoderm Expression Oscillates in phase with Axin2 in the Somitogenesis Clock of Mice. Dev Dyn, 235: 3177-3183, 2006.

Fisher, DA, Kivimäe, S, Hoshino, J, Suriben, R, Martin, P-M, Baxter, N, Cheyette, BNR. Three Dact Gene Family Members are Expressed During Embryonic Development and in the Adult Brains of Mice. Dev Dyn Mouse Development Special Issue, 235: 2620-2630, 2006.

Kovoor, A, Seyffarth, P, Ebert, J, Barghshoon, S, Ching-Kang, C, Schwarz, S, Axelrod, JD, Cheyette, BNR, Simon, MI, Lester, HA, and Schwarz, J. D2-dopamine Receptors Colocalize RGS9-2 via the RGS9 DEP domain and RGS9 knockout mice develop dyskinesias associated with dopamine pathways. J Neurosci. 25: 2157-65, 2005.

Cheyette, BNR, Waxman, JS, Miller, JR, Takemaru, KI, Sheldahl, LC, Khlebtsova, N, Fox, EP, Earnest, T, and Moon, RT. Dapper, a Dishevelled-Associated Antagonist of ß-catenin and JNK Signaling, is required for Notochord Formation, Developmental Cell. 2: 449-461, 2002.

Cheyette, BNR, Green, PJ, Martin, K, Garren, H, Hartenstein, V, and Zipursky, SL. (1994) The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron. 12: 977-996, 1994.

Benjamin Cheyette, MD/Ph.D.