Research Interests
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 characterized new mutants, taking advantage of the ability to visualize growing axons in live zebrafish embryos.
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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.
Ungos, J.M., Karlstrom, R.O. , and Raible, D.W. 2003.
Hedgehog
signaling is directly required for the development of zebrafish dorsal root ganglia neurons. Development. 130: 5351-5362.
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 and divergent requirements
for gli genes in vertebrate development. Development. 130:
549-1564.
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., Moss, J.B., Sbrogna, J.L., Karlstrom, R.O., and
Moss, L.G. 2002.
Sonic
hedgehog Is Required Early in Pancreatic Islet Development. Developmental
Biology, 2002 Apr 1 244(1): 75-84.
Kondoh, H., Ukhikawa, M., Yoda, 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., Trowe, T. and Bonhoeffer, F. 1997. Genetic analysis of
axon guidance in the zebrafish. Trends in Neurosciences 20: 3-8.
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.
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