Professor of Neurobiology and Anatomy
Director of the Neuroscience Program
B.A. University of California, Berkeley
Ph.D. University of California, San Diego
Rich Dorsky's Lab Page
Rich Dorsky's PubMed Literature Search
Molecular Biology Program
During development of the central nervous system (CNS), cells are influenced by their environment to adopt specific fates. These environmental signals are crucial for the correct patterning of cell types and their subsequent functional connections. My laboratory is studying the role of the Wnt/β-catenin signaling pathway in CNS cell fate specification. We use zebrafish as a model organism, focusing on the regulation of Wnt/β-catenin target genes in the CNS by a family of transcription factors called Tcf proteins. Tcfs are required for β-catenin to regulate transcription, and can act as repressors or activators of target genes depending on the state of Wnt signaling.
SPINAL CORD NEUROGENESIS
We are interested in the functions of Wnt signaling and Tcf function in spinal cord
development and regeneration. Our work has shown that Tcf7l1 inhibits the differentiation
of spinal cord neural progenitors during embryogenesis. We have also shown that following
transection of the larval spinal cord, Wnt signaling is required for radial glia to
generate new neurons.
One current project in the lab is testing the hypothesis that Tcf7l1 maintains the quiescence of radial glial neural progenitors through repression of transcriptional targets.
This function may be critical for stem cell-mediated regeneration.
A second project is determining the mechanism downstream of Wnt signaling that mediates neurogenesis following injury. We are also investigating whether new neurons are required for the recovery of sensory and motor function.
This work focuses on the role of Wnt and Lef1 activity in the differentiation of neural
progenitors in the posterior hypothalamus. This region of the brain maintains Wnt
activity and continues to produce neurons throughout life, suggesting that Wnt-regulated
neurogenesis plays an important role in the adult brain.
Evolutionary conservation of Wnt-responsive neurons in the hypothalamus suggests that a common behavioral function may be regulated by this pathway. To investigate this possibility, we are using genetic approaches to perturb Wnt signaling and to modulate hypothalamic neurons in vivo. We are also identifying Lef1 target genes in the zebrafish and mouse hypothalamus, and determining their function in neurogenesis and behavior.
McPherson AD, Barrios JP, Luks-Morgan SJ, Manfredi JP, Bonkowsky JL, Douglass AD, Dorsky RI. Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers after Cell Ablation. Current Biology 26 (2016) 263-9.
Duncan RN, Xie Y, McPherson AD, Taibi AV, Bonkowsky JL, Douglass AD, Dorsky RI. Hypothalamic radial glia function as self-renewing neural progenitors in the absence of Wnt/ß-catenin signaling. Development 143 (2016) 45-53.
- Briona LK, Poulain FE, Mosimann C, Dorsky RI. Wnt/ß-catenin signaling is required for radial glial neurogenesis following spinal cord injury. Developmental Biology 403 (2015) 15-21.
- Otsuna H, Hutcheson DA, Duncan RN, McPherson AD, Scoresby AN, et al. High-resolution analysis of central nervous system expression patterns in zebrafish Gal4 enhancer-trap lines. Developmental dynamics : an official publication of the American Association of Anatomists 244 (2015) 785-96.
- Briona LK and Dorsky RI. Radial glial progenitors repair the zebrafish spinal cord following transection. Experimental Neurology 256 (2014) 81-92.
- Wang X, Kopinke D, Lin J, McPherson AD, Duncan RN, Otsuna H, Moro E, Hoshijima K, Grunwald DJ, Argenton F, Chien CB, Murtaugh LC and Dorsky RI. Wnt Signaling Regulates Postembryonic Hypothalamic Progenitor Differentiation. Developmental Cell 23 (2012) 624-636.
- Bonner J, Letko M, Nikolaus OB, Krug L, Cooper A, Chadwick B, Conklin P, Lim A, Chien CB and Dorsky RI. Midline crossing is not required for subsequent pathfinding decisions in commissural neurons. Neural Development 7 (2012) 18.
- Kim HS and Dorsky RI. Tcf7l1 is required for spinal cord progenitor maintenance. Developmental Dynamics 240 (2011) 2256-64.
- Lin J, Wang X and Dorsky RI. Progenitor expansion in apc mutants is mediated by Jak/Stat signaling. BMC Developmental Biology 11 (2011) 73.
- Gribble SL, Kim HS, Bonner J, Wang X and Dorsky RI. Tcf3 inhibits spinal cord neurogenesis by regulating sox4a expression. Development 136 (2009) 781-9.
- Wang X, Lee JE and Dorsky RI. Identification of Wnt-responsive cells in the zebrafish hypothalamus. Zebrafish 6 (2009) 49-58.
- Veien ES, Rosenthal JS, Kruse-Bend RC, Chien CB and Dorsky RI. Canonical Wnt signaling is required for the maintenance of dorsal retinal identity. Development 135 (2008) 4101-11.
- Bonner, J, Gribble SL, Veien ES, Nikolaus OB, Weidinger G and Dorsky RI. Distinct pathways mediate patterning and proliferation in the dorsal spinal cord downstream of canonical Wnt signaling. Developmental Biology 313 (2008) 398-407.
- Gribble SL, Nikolaus OB and Dorsky RI. Regulation and function of Dbx genes in the zebrafish spinal cord. Developmental Dynamics 236 (2007) 3472-83.
- Nyholm MK, Wu S, Dorsky RI and Grinblat Y. The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum. Development 134 (2007) 735-746.
- Lee J, Wu S, Goering LM and Dorsky RI. Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis. Development 133 (2006) 4451-4461.
- Veien ES, Grierson MJ, Saund RS and Dorsky RI. Expression pattern of zebrafish tcf7 suggests unexplored domains of Wnt/beta-catenin activity. Developmental Dynamics 233 (2005) 233-239.
- Lewis JL, Bonner J, Modrell M, Ragland JW, Moon RT, Dorsky RI and Raible DW. Reiterated Wnt signaling during zebrafish neural crest development. Development 131 (2004) 1299-1308.
- Dorsky RI, Itoh M, Moon RT and Chitnis A. Two tcf3 genes cooperate to pattern the zebrafish brain. Development 130 (2003) 1937-1947.
- Dorsky RI, Sheldahl LC and Moon RT. A Transgenic Lef1/β-catenin-Dependent Reporter is Expressed in Spatially -Restricted Domains Throughout Zebrafish Development. Developmental Biology 241 (2002) 229-237.
- Dorsky RI, Raible DW and Moon RT. Signaling pathways and neural crest fate specification. BioEssays 22 (2000) 708-716.