ZFIN ID: ZDB-LAB-990302-7
Karlstrom Lab
PI/Director: Karlstrom, Rolf
Contact Person: Karlstrom, Rolf
Email: karlstrom@bio.umass.edu
URL: http://www.bio.umass.edu/biology/faculty/karlstrom.phtml
Address: Department of Biology University of Massachusetts 611 North Pleasant Street Amherst, MA 01003 USA
Country: United States
Phone: (413) 577-3456
Fax: (413) 577-3243
Line Designation: umz

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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.

Osgood, Marcey Graduate Student Ozacar, Ayse Tuba Graduate Student Thomas, Jeanne Research Staff
Bennet, Judy Fish Facility Staff

Male, I., Ozacar, A.T., Fagan, R.R., Loring, M.D., Loring, M.D., Shen, M.C., Pace, V.A., Devine, C.A., Lawson, G.E., Lutservitz, A., Karlstrom, R.O. (2020) Hedgehog signaling regulates neurogenesis in the larval and adult zebrafish hypothalamus. eNeuro. 7(6):
Navon, D., Male, I., Tetrault, E.R., Aaronson, B., Karlstrom, R.O., Albertson, R.C. (2020) Hedgehog signaling is necessary and sufficient to mediate craniofacial plasticity in teleosts. Proceedings of the National Academy of Sciences of the United States of America. 117(32):19321-19327
Tonyushkina, K., Krug, S., Ortiz-Toro, T., Mascari, T., Karlstrom, R. (2017) Low thyroid hormone levels disrupt thyrotrope development. Endocrinology. 158(9):2774-2782
Breves, J.P., McCormick, S.D., and Karlstrom, R.O. (2014) Prolactin and teleost ionocytes: New insights into cellular and molecular targets of prolactin in vertebrate epithelia. General and comparative endocrinology. 203C:21-28
Tonyushkina, K.N., Shen, M.C., Ortiz-Toro, T., and Karlstrom, R.O. (2014) Embryonic exposure to excess thyroid hormone causes thyrotrope cell death. J. Clin. Invest.. 124(1):321-327
Shen, M., Ozacar, A.T., Osgood, M., Boeras, C., Pink, J., Thomas, J., Kohtz, J., and Karlstrom, R.O. (2013) Heat-shock–mediated conditional regulation of hedgehog/gli signaling in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 242(5):539-49
Breves, J.P., Serizier, S.B., Goffin, V., McCormick, S.D., and Karlstrom, R.O. (2013) Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill. Molecular and Cellular Endocrinology. 369(1-2):98-106
Choi, W.Y., Gemberling, M., Wang, J., Holdway, J.E., Shen, M.C., Karlstrom, R.O., and Poss, K.D. (2013) In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration. Development (Cambridge, England). 140(3):660-666
Bergeron, S.A., Tyurina, O.V., Miller, E., Bagas, A., and Karlstrom, R.O. (2011) Brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish. Development (Cambridge, England). 138(1):75-85
Barresi, M.J., Burton, S., Dipietrantonio, K., Amsterdam, A., Hopkins, N., and Karlstrom, R.O. (2010) Essential genes for astroglial development and axon pathfinding during zebrafish embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists. 239(10):2603-2618
Gates, K.P., Mentzer, L., Karlstrom, R.O., and Sirotkin, H.I. (2010) The transcriptional repressor REST/NRSF modulates hedgehog signaling. Developmental Biology. 340(2):293-305
Placinta, M., Shen, M.C., Achermann, M., and Karlstrom, R.O. (2009) A laser pointer driven microheater for precise local heating and conditional gene regulation in vivo. Microheater driven gene regulation in zebrafish. BMC Developmental Biology. 9:73
Wang, Z., Glenn, H., Brown, C., Valavanis, C., Liu, J.X., Seth, A., Thomas, J.E., Karlstrom, R.O., and Schwartz, L.M. (2009) Regulation of muscle differentiation and survival by Acheron. Mechanisms of Development. 126(8-9):700-709
Devine, C.A., Sbrogna, J.L., Guner, B., Osgood, M., Shen, M.C., and Karlstrom, R.O. (2009) A dynamic Gli code interprets Hh signals to regulate induction, patterning, and endocrine cell specification in the zebrafish pituitary. Developmental Biology. 326(1):143-154
Guner, B., Ozacar, A.T., Thomas, J.E., and Karlstrom, R.O. (2008) Graded hedgehog and fibroblast growth factor signaling independently regulate pituitary cell fates and help establish the pars distalis and pars intermedia of the zebrafish adenohypophysis. Endocrinology. 149(9):4435-4451
Bergeron, S.A., Milla, L.A., Villegas, R., Shen, M.C., Burgess, S.M., Allende, M.L., Karlstrom, R.O., and Palma, V. (2008) Expression profiling identifies novel Hh/Gli-regulated genes in developing zebrafish embryos. Genomics. 91(2):165-177
Guner, B., and Karlstrom, R.O. (2007) Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube. Gene expression patterns : GEP. 7(5):596-605
Cerda, G.A., Thomas, J.E., Allende, M.L., Karlstrom, R.O., and Palma, V. (2006) Electroporation of DNA, RNA, and morpholinos into zebrafish embryos. Methods (San Diego, Calif.). 39(3):207-211
Seth, A., Culverwell, J., Walkowicz, M., Toro, S., Rick, J.M., Neuhauss, S.C., Varga, Z.M., and Karlstrom, R.O. (2006) belladonna/(lhx2) is required for neural patterning and midline axon guidance in the zebrafish forebrain. Development (Cambridge, England). 133(4):725-735
Barresi, M.J., Hutson, L.D., Chien, C.B., and Karlstrom, R.O. (2005) Hedgehog regulated Slit expression determines commissure and glial cell position in the zebrafish forebrain. Development (Cambridge, England). 132(16):3643-3656
Vanderlaan, G., Tyurina, O.V., Karlstrom, R.O., and Chandrasekhar, A. (2005) Gli function is essential for motor neuron induction in zebrafish. Developmental Biology. 282(2):550-570
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(2):537-556
Feng, J., White, B., Tyurina, O.V., Guner, B., Larson, T., Lee, H.Y., Karlstrom, R.O., and Kohtz, J.D. (2004) Synergistic and antagonistic roles of the Sonic hedgehog N- and C-terminal lipids. Development (Cambridge, England). 131(17):4357-4370
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 (Cambridge, England). 131(11):2521-2532
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 (Cambridge, England). 130(22):5351-5362
Karlstrom, R.O., Tyurina, O.V., 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 (Cambridge, England). 130(8):1549-1564
Sbrogna, J.L., Barresi, M.J., and Karlstrom, R.O. (2003) Multiple roles for Hedgehog signaling in zebrafish pituitary development. Developmental Biology. 254(1):19-35
Culverwell, J. and Karlstrom, R.O. (2002) Making the connection: retinal axon guidance in the zebrafish. Seminars in cell & developmental biology. 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. 244(1):75-84
Kondoh, H., Uchikawa, 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(2):165-174
Karlstrom, R.O., Talbot, W.S., and Schier, A.F. (1999) Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning. Genes & Development. 13:388-393
Karlstrom, R.O., Trowe, T., and Bonhoeffer, F. (1997) Genetic analysis of axon guidance and mapping in the zebrafish. Trends in neurosciences. 20(1):3-8
Baier, H., Klostermann, S., Trowe, T., Karlstrom, R.O., Nüsslein-Volhard, C., and Bonhoeffer, F. (1996) Genetic dissection of the retinotectal projection. Development (Cambridge, England). 123:415-425
Brand, M., Heisenberg, C.P., Warga, R.M., Pelegri, F., Karlstrom, R.O., Beuchle, D., Picker, A., Jiang, Y.J., Furutani-Seiki, M., van Eeden, F.J., 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 midline and general body shape during zebrafish embryogenesis. Development (Cambridge, England). 123:129-142
Karlstrom, R.O. and Kane, D.A. (1996) A flipbook of zebrafish embryogenesis. Development (Cambridge, England). 123:461
Karlstrom, R.O., Trowe, T., Klostermann, S., Baier, H., Brand, M., Crawford, A.D., Grunewald, B., Haffter, P., Hoffman, H., Meyer, S.U., Muller, B.K., Richter, S., van Eeden, F.J., Nüsslein-Volhard, C., and Bonhoeffer, F. (1996) Zebrafish mutations affecting retinotectal axon pathfinding. Development (Cambridge, England). 123:427-438
Trowe, T., Klostermann, S., Baier, H., Granato, M., Crawford, A.D., Grunewald, B., Hoffman, H., Karlstrom, R.O., Meyer, S.U., Muller, B., 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 (Cambridge, England). 123:439-450