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Josh Bonkowsky

Associate Professor of Pediatrics
Adjunct Associate Professor of Neurobiology and Anatomy
Director, Pediatric Neurology Research

Developmental Neurobiology
Neurobiology of Disease
Molecular Neuroscience



B.A. 1991, Harvard College; M.D., Ph.D. 2000, University of California, San Diego, 2003-2006, Postdoctoral Fellowship, University of Utah

Transgenic zebrafish; with labeling in the dopamine neurons.
Normal motor development requires input from these neurons.



Development of connectivity, axons and synapses. Role and effects of hypoxia on CNS development. Leukodystrophies.

Our research is centered on studying the development of CNS connectivity and neurodevelopmental disorders. Neurodevelopmental disorders are very common, but poorly understood in terms of their pathophysiology and effects on CNS development. To address these disorders, we are taking both a gene-specific approach, as well as a non-biased strategy. We are currently focused on three main areas:

1. Developmental functions of human disease genes.
We are studying the role of several human disease genes on CNS development. For example, the gene FOXP2 controls the development of language in humans, and we are studying its role in regulation of axon fasciculation and axon pathfinding. We are also studying genes involved in human leukodystrophies, and developing a zebrafish model for developing novel therapies.

2. Development of the basal ganglia.
The basal ganglia play a critical role in the CNS, and dysfunction underlie many common neurological disorders (cerebral palsy, Parkinson's, and Huntington's, for example). We have developed unique transgenic lines which specifically label subsets of basal ganglia neurons, allowing us to perform live visualization of their development. These transgenic lines are allowing us to analyze which genes are necessary for the development of basal ganglia connectivity, and the role of genes such as GBA in the development of Parkinson's disease. Finally, we are determining what genes control reorganization of neural circuits following CNS injury.

3. Novel techniques for analysis of CNS connectivity.
Understanding how the CNS is wired is extremely complex. We are developing novel technologies to analyze how genetically distinct neurons recognize and target specific connections, and what the functional relevance of these connections are. The first technique, the use of Gal80 in vertebrates, is in press (Fujimoto et al., 2011). The second technique uses an innovative method to permit trans-synaptic labeling in live animals.

Selected Publications:

Milash, B., Gao, J., Stevenson, T.J., Son, J.H., Dahl, T., and Bonkowsky, J.L. (2016) Temporal Dysynchrony in brain connectivity gene expression following hypoxia. BMC Genomics, May 4;17(1):334.

Sivachenko, A., Gordon, H.B., Kimball, S.S., Gavin, E.J., Bonkowsky, J.L., and Letsou, A. (2016) Neurodegeneration in a Drosophila model of Adrenoleukodystrophy: the roles of the bubblegum and double bubble acyl-CoA synthetases. Disease Models and Mechanisms, Feb 18. pii: dmm.022244. [Epub ahead of print]

Bonkowsky, J.L. (2016) Shedding light on the leukodystrophies. Developmental Medicine and Child Neurology, Feb 15. doi: 10.1111/dmcn.13019. [Epub ahead of print]

McPherson, A.D., Barrios, J.P., Luks-Morgan, S.J., Manfredi, J.P., Bonkowsky, J.L., Douglass, A.D., and Dorsky, R.I. (2016) Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers after Cell Ablation. Current Biology, Jan 25;26(2):263-269.

Son, J.H., Keefe, M.D., Stevenson, T.J., Barrios, J.P., Anjewierden, S., Newton, J.B., Douglass, A.D., and Bonkowsky, J.L. (2016) Transgenic FingRs for Live Mapping of Synaptic Dynamics in Genetically-Defined Neurons. Scientific Reports (Nature), Jan 5;6:18734.

Xing, L., Son, J.H., Stevenson, T.J., Lillesaar, C., Bally-Cuif, L., Dahl, T., and Bonkowsky, J.L. (2015) A Serotonin Circuit Acts as an Environmental Sensor to Mediate Midline Axon Crossing through EphrinB2. Journal of Neuroscience, Nov 4;35(44):14794-14808.

Samuel, R., Stephenson, R., Roy, P., Pryor, R., Zhou, L., Bonkowsky, J.L.*, and Gale, B.K.* (2015) Microfluidic-aided genotyping of zebrafish in the first 48 h with 100% viability. Biomedical Microdevices, [in press].

Butterfield, R.J., Stevenson, T.J., Xing, L., Newcomb, T.M., Nelson, B., Zeng, W., Li, X., Lu, H.M., Lu, H., Farwell Gonzalez, K.D., Wei, J.P., Chao, E.C., Prior, T.W., Snyder, P.J., Bonkowsky, J.L., and Swoboda, K.J. (2014) Congenital Lethal Motor Neuron Disease with a Novel Defect in Ribosome Biogenesis. Neurology, Apr 15;82(15):1322-1330.

Xing, L., Quist, T., Stevenson, T., Dahlem, T., and Bonkowsky, J.L. (2014) Rapid and Efficient Zebrafish Genotyping Using PCR with High-resolution Melt Analysis. J. Vis. Exp., Feb 5;(84):e51138.

Iwasaki, K., Taguchi, M., Bonkowsky, J.L., and Kuwada, J.Y. (2013) Expression of arginine vasotocin receptors in the developing zebrafish CNS. Gene Expr Patterns, Jul 2;13(8):335-342.

Schweitzer, J., Löhr, H., Bonkowsky, J.L., Hübscher, K., and Driever, W. (2013) Sim1a and Arnt2 contribute to hypothalamo-spinal axon guidance by regulating Robo2 activity via a Robo3-dependent mechanism. Development, Jan;140(1):93-106.

Xing, L., Hoshijima, K., Grunwald, D.J., Fujimoto, E., Quist, T.S., Sneddon, J., Chien, C.B., Stevenson, T.J., and Bonkowsky, J.L. (2012) Zebrafish foxP2 zinc finger nuclease mutant has normal axon pathfinding. PLoS One, 7(8):e43968.

Lambert, A.M., Bonkowsky, J.L., and Masino, M.A. (2012) The dopaminergic diencephalospinal tract mediates a developmental switch in the locomotor pattern of larval zebrafish. Journal of Neuroscience, 32:13488-13500.

Stevenson, T.J., Trinh, T., Kogelschatz, C., Fujimoto, E., Lush, M.E., Piotrowski, T., Brimley, C.J., and Bonkowsky, J.L. (2012) Hypoxia disruption of vertebrate CNS pathfinding through EphrinB2 is rescued by magnesium. PLoS Genetics, April.

Lakhina, V., Maraccio, C., Shao, X., Lush, M., Jain, R., Fujimoto, E., Bonkowsky, J., Granato, M., and Raper, J. (2012) Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb. Journal of Neuroscience.

Gutnick, A., Blechman, J., Kaslin, J., Affolter, M., Bonkowky, J.L., and Levkowitz, G. (2011) The hypothalamic neuropeptide oxytocin is required for formation of the neuro-vascular interface of the pituitary. Developmental Cell, 18:642-654.

Fujimoto, E., Gaynes, B., Brimley, C.J., Chien, C.B., and Bonkowsky, J.L. (2011) Gal80 Intersectional Regulation of Cell-Type Specific Expression in Vertebrates. Developmental Dynamics, Oct;240(10):2324-2334.

Fujimoto, E., Stevenson, T.J., Chien, C.-B., and Bonkowsky, J.L. (2011) Identification of a Dopaminergic Enhancer Indicates Complexity in Vertebrate Dopamine Neuron Phenotype Specification. Developmental Biology, Jan 27. [Epub ahead of print].

Kastenhuber, E., Kern, U., Bonkowsky, J.L., Chien, C.-B., Driever, W., and Schweitzer, J. (2009) Netrin-DCC, Robo-Slit and HSPGs coordinate lateral positioning of longitudinal dopaminergic diencephalospinal axons. Journal of Neuroscience, 29:8914-8926.

Bonkowsky, J.L., Wang, X., Fujimoto, E., Lee, J.E., Chien, C.B., and Dorsky, R.I. (2008) Domain-specific regulation of foxP2 CNS expression by lef1. BMC Dev Biol, Oct 24; 8:103.

Bonkowsky, J.L., Filloux, F.M., and Warner, J.E. (2007) Splenial Corpus Callosum Lesion and Hemifield Visual Color Anomia Associated With Intracranial Hypertension. Journal of Child Neurology, 22:1132-1134.

Bonkowsky, J.L., and Chien, C.-B. (2005) Isolation and cloning of zebrafish foxP2. Developmental Dynamics, 234:740-746.

Bonkowsky, J.L., Bohnsack, J.F., Pennington, M.J., Viskochil, D., and Thompson, J.A. (2004) Leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia (LACH) in two brothers: a novel syndrome? American Journal of Medical Genetics, 128:52-56.

Bonkowsky, J.L., Johnson, J., Carey, J., Smith, A.D., and Swoboda, K. (2003) An infant with primary tooth loss and palmar hyperkeratosis: a novel mutation in the NTRK1 gene causing congenital insensitivity to pain with anhidrosis. Pediatrics, 112:e237-241.

Yoshikawa*, S., Bonkowsky*, J.L., Kokel, M., Shyn, S., and Thomas, J.B. (2001) The Derailed guidance receptor does not require kinase activity in vivo. Journal of Neuroscience, 21: RC119.

Bonkowsky*, J.L, Yoshikawa*, S., O'Keefe, D.D., Scully, A.L., and Thomas, J.B. (1999) Axon routing across the midline controlled by the Drosophila Derailed receptor. Nature, 402:540-544.

Bonkowsky, J.L., and Thomas, J.B. (1998) Cell-type specific modular regulation of derailed in the Drosophila nervous system. Mechanisms of Development, 82:181-184.

Oates, A.C., Bonkowsky, J.L., Irvine, D.V., Kelly, L.E., Thomas, J.B., and Wilks, A.F. (1998) Embryonic expression and activity of doughnut, a second RYK homolog in Drosophila. Mechanisms of Development, 78:165-169.

Last Updated: 3/29/17