Rolf O. Karlstrom

Associate Professor of Biology, University of Massachusetts

Email: karlstrom@bio.umass.edu
R. Karlstorm Biology Web Site
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Ph.D.: University of Utah
Postdoctoral Training: Max-Planck-Institute, Tubingen, Germany; Skirball Institute, New York University School of Medicine

Developmental Neurobiology: Axon Guidance and Forebrain Patterning

As the brain develops, neurons extend axons over relatively vast distances to their targets. My laboratory uses zebrafish as a simple vertebrate system to study how axons navigate through the developing brain. Accessible and rapid early development, in combination with the ability to transplant cells between embryos, express genes both transiently and transgenically, and do genetic screens, makes zebrafish a powerful model system for the study of axon guidance.

We are characterizing several mutations that disrupt the ability of retinal axons to grow across the forebrain. Using a synteny cloning approach, we have identified the genes affected by the mutations you-too (yot) and detour (dtr). Both loci encode members of the gli family of transcription factors, proteins that are targets of early differentiation signals mediated by the secreted morphogen sonic hedgehog. These mutations disrupt cell differentiation in the ventral forebrain, including the pituitary. One focus of the lab is to understand the cellular cues disrupted in yot and dtr that normally guide axons across the forebrain, and to understand how midline signals direct the differentiation of these cells. A related goal is to determine the molecular and cellular mechanisms underlying axon defects in two other, more specific retinotectal mutations named belladonna and umleitung.

We ultimately hope to understand the cues that guide axons through their entire journey from eye to tectum. Toward this end, the lab will generate and characterize new mutants, taking advantage of the ability to visualize growing axons in live zebrafish embryos.

Representative publications:

Cerda, G.A., Thomas, J.E., Allende, M.A., Karlstrom, R.O. , Palma, V. (in press). Electroporation of DNA, RNA, and morpholinos into zebrafish embryos. Methods .

Barresi, M.J., Hutson, L. Chien, C-B., and Karlstrom, R.O . (2005) Hedgehog regulated Slit expression determines commissure and glial cell position in the zebrafish forebrain. Development, 132(16); 3643-56

Vanderlaan, G.M., Tyurina, O.V., Karlstrom, R.O. , and Chandrasekhar, A., (2005) Gli Function is Essential for Motor Neuron Induction in Zebrafish. Developmental Biology, 282(2);550-70

Tyurina, O.V., Guner, B., Popova, E., Feng, J., Schier, A.F., Kohtz, J.D., and Karlstrom, R.O . (2005) Zebrafish Gli3 functions as both an activator and a repressor in Hedgehog signaling. Developmental Biology. 277;537- 556

Feng, J., White, B., Tyurina, O., Guner, B., Larson, T., Lee, H., Karlstrom, R. O ., and Kohtz, J. (2004). Synergistic and antagonistic roles of the Sonic hedgehog N and C-terminal lipids. Development 131(17):4357-70.

Sekimizu, K, Nishioka, N, Sasaki, H, Takeda, H, Karlstrom, R.O . and Kawakami, A. (2004).. The zebrafish iguana locus encodes Dzip1, a novel zinc finger protein required for proper regulation of hedgehog signaling. Development . 131, 2521.

Sbrogna, J.L., Barresi, M.J.F., and Karlstrom, R.O. (2003) Multiple roles
for hedgehog signaling in zebrafish pituitary development. Developmental
Biology. 254(1):19-35.

Karlstrom, R.O., Tyurina, O., Kawakami, A., Nishioka, N., Talbot, W.S.,
Sasaki, H., and Schier, A.F. (2003) Genetic analysis of zebrafish gli1 and
gli2 reveals divergent requirements for gli genes in vertebrate
development. Development. 130, 1549-1564

Culverwell, J, and Karlstrom, R.O. (2002) Making the connection: Retinal
axon guidance in the zebrafish. Sem. Cell and Developmental Biol.
13(6):497-506.

diIorio, P. J., J. B. Moss, J. L. Sbrogna, R. O. Karlstrom and L. G. Moss (2002). "Sonic hedgehog is required early in pancreatic islet development." Dev Biol 244(1): 75-84.

Kondoh, H., Ukhikawa, M., Yoda, H., Takeda, H., Furutani-Seiki, M., and Karlstrom, R.O. (2000) Zebrafish mutations in gli-mediated hedgehog signaling lead to lens transdifferentiation from the adenohypophysis anlage. Mechanisms of Development 96: 165-174.

Karlstrom, R.O., Talbot, W.S. and Schier, A.F. (1999) Synteny cloning of zebrafish you-too: Mutations in the hedgehog target gli2 affect ventral forebrain patterning. Genes and Development 13, 388-393.

Karlstrom, R.O. and Kane, D.A. (1996) A time-lapse flip-book of zebrafish development. Development 123, 2-460.

Karlstrom, R.O., et al. (1996) Zebrafish mutations affecting retinotectal axon pathfinding. Development 123, 427-438.