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.

 

 

Rolf O. Karlstrom

Developmental Neurobiology: Axon Guidance and Forebrain Patterning  

Ph.D.: University of Utah
Postdoctoral Training: Max-Planck-Institute, Tübingen, Germany; Skirball Institute, New York University School of Medicine

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.

 

Karlstrom Lab Homepage

Zebrafish Movie

Zebrafish Facility

 

Representative Publications:

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.

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. MEDLINE

Karlstrom, R.O., Trowe, T. and Bonhoeffer, F. (1997) Genetic analysis of axon guidance in the zebrafish. Trends in Neurosciences 20, 3-8. MEDLINE

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

Karlstrom, R.O., Trowe, T., Klostermann, S., Baier, H., Brand, M., Crawford, A.D., Grunewald, B., Haffter, P., Hoffmann, H., Meyer, S.U., Müller, B., Richter, S., van Eeden, F.J.M., Nüsslein-Volhard, C., and Bonhoeffer, F. (1996) Zebrafish mutations affecting retinotectal axon pathfinding. Development 123, 427-438. MEDLINE

Baier, H., Klostermann, S., Trowe, T., Karlstrom, R.O., Nüsslein-Volhard, C. and Bonhoeffer, F. (1996). Genetic dissection of the retinotectal projection. Development 123, 415-425.

Brand, M., Heisenberg, C.-P., Beuchle, D., Jiang, Y.-J., Karlstrom, R.O., Warga, R.M., Pelegri, F., van Eeden, F.J.M., Furutani-Seiki, M., Granato, M., Haffter, P., Hammerschmidt, M., Kane, D. A., Kelsh, R.N., Mullins, M.C., Odenthal, J. and Nüsslein-Volhard, C. (1996). Mutations affecting development of the spinal chord and general body shape during zebrafish embryogenesis. Development 123, 129-142.

Trowe, T., Klostermann, S., Baier, H., Granato, M., Crawford, A.D., Grunewald, B., Hoffmann, H., Karlstrom, R.O., Meyer, S.U., Richter, S., Nüsslein-Volhard, C. and Bonhoeffer, F. (1996). Mutations disrupting the ordering and topographic mapping of axons in the retinotectal projection of the zebrafish, Danio rerio. Development 123, 439-450.

Karlstrom, R.O., Wilder, L.P., and Bastiani, M.J. (1993) Lachesin: An immunoglobulin superfamily protein whose expression correlates with neurogenesis and axon outgrowth in grasshopper embryos. Development 118, 509-522.

Karlstrom, R.O. (1993). Characterization and cloning of Lachesin: a novel immunoglobulin superfamily molecule whose expression correlates with segmentation and neurogenesis during insect development. Ph.D. Dissertation. University of Utah.

Bastiani, M.J., de Couet, H.G., Quinn, J.M.A., Kotrla, K.J., Karlstrom, R.O., Goodman, C.S., and Ball, E.E. (1992) Transient and dynamic expression of the MEG protein during development of the grasshopper embryo. Developmental Biology 154, 129-142.

Seaver, E.C., Karlstrom, R.O., and Bastiani, M.J. (1991) The restricted spatial and temporal expression of a nervous-system-specific antigen involved in axon outgrowth during development of the grasshopper. Development 111, 881-893.

Zafaralla, G.C., Ramilo, C., Gray, W.R., Karlstrom, R.O., Olivera, B.M., and Cruz, L. (1988) Phylogenetic specificity of cholinergic ligands: alpha-conotoxin S1. Biochemistry 27, 7102-7105.

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