Professor of Neurobiology and Anatomy
The Dorsky Lab
Signaling pathways in zebrafish neural cell fate determination
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.
Briona, L.K., Poulain, F.E., Mosimann, C., and Dorsky, R.I. (2015) Wnt/ß-catenin signaling is required for radial glial neurogenesis following spinal cord injury. Developmental Biology, 403:15-21.
Otsuna, H., Hutcheson, D.A., Duncan, R.N., McPherson, A.D., Scoresby, A.N., et al. (2015) 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, 244:785-796.
Briona, L.K., and Dorsky, R.I. (2014) Radial glial progenitors repair the zebrafish spinal cord following transection. Exp Neurol, 256:81-92.
Kruse-Bend, R., Rosenthal, J., Quist, T.S., Veien, E.S., Fuhrmann, S., Dorsky, R.I., and Chien, C.B. (2012) Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Dev. Biol., 371:57-65.
Wang, X., Kopinke, D., Lin, J., McPherson, A.D., Duncan, R.N., Otsuna, H., Moro, E., Hoshijima, K., Grunwald, D.J., Argenton, F., Chien, C.B., Murtaugh, L.C., and Dorsky, R.I. (2012) Wnt signaling regulates post-embryonic hypothalamic progenitor differentiation. Developmental Cell, 23:624-636.
Bonner, J., Letko, M., Nikolaus, O.B., Krug, L., Cooper, A., Chadwick, B., Conklin, P., Lim, A., Chien, C.B., and Dorsky, R.I. (2012) Midline crossing is not required for subsequent pathfinding decisions in commissural neurons. Neural Development, 7:18.
Kim, H.S., and Dorsky, R.I. (2011) Tcf7l1 is required for spinal cord progenitor maintenance. Developmental Dynamics, 240:2256-2264.
Lin, J., Wang, X., and Dorsky, R.I. (2011) Progenitor expansion in apc mutants is mediated by Jak/Stat signaling. BMC Developmental Biology, 11:73.
Wang, X., Lee, J.E., and Dorsky, R.I. (2009) Identification of Wnt-responsive cells in the zebrafish hypothalamus. Zebrafish, 6:49-58.
Gribble, S.L., Kim, H.S., Bonner, J., Wang, X., and Dorsky, R.I. (2009) Tcf3 inhibits spinal cord neurogenesis by regulating sox4a expression. Development, 136:781-789.
Veien, E.S., Rosenthal, J.S., Kruse-Bend, R.C., Chien, C.B., and Dorsky, R.I. (2008) Canonical Wnt signaling is required for the maintenance of dorsal retinal identity. Development, 135:4101-4111.
Bonner, J., Gribble, S.L., Veien, E.S., Nikolaus, O.B., Weidinger, G., and Dorsky, R.I. (2008) Distinct pathways mediate patterning and proliferation in the dorsal spinal cord downstream of canonical Wnt signaling. Developmental Biology, 313:398-407.
Gribble, S.L., Nikolaus, O.B., and Dorsky, R.I. (2008) Regulation and function of Dbx genes in the zebrafish spinal cord. Developmental Dynamics, 236:3472-3483.
Nyholm, M.K., Wu, S., Dorsky, R.I., and Grinblat, Y. (2007) The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum. Development, 134:735-746.
Lee, J., Wu, S., Goering, L.M., and Dorsky, R.I. (2006) Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis. Development, 133:4451-4461.
Veien, E.S., Grierson, M.J., Saund, R.S., and Dorsky, R.I. (2005) Expression pattern of zebrafish tcf7 suggests unexplored domains of Wnt/β-catenin activity. Dev Dyn., 233:233-239.
Lewis, J.L., Bonner, J., Modrell, M., Ragland, J.W., Moon, R.T., Dorsky, R.I., and Raible, D.W. (2004) Reiterated Wnt signaling during zebrafish neural crest development. Development, Mar;131(6):1299-1308.
Dorsky, R.I., Itoh, M., Moon, R.T., and Chitnis, A. (2003) Two tcf3 genes cooperate to pattern the zebrafish brain. Development, 130:1937-1947.
Dorsky, R.I., Sheldahl, L.C. and Moon, R.T. (2002) A Transgenic Lef1/β-catenin-Dependent Reporter is Expressed in Spatially -Restricted Domains Throughout Zebrafish Development. Developmental Biology, 241:229-237.
Dorsky, R.I., Raible, D.W. and Moon, R.T. (2000) Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway. Genes and Development, 14:158-162.
Dorsky, R.I., Moon, R.T. and Raible, D.W. (1998) Control of neural crest cell fate by the Wnt signalling pathway. Nature, 396:370-373.