ZFIN ID: ZDB-PERS-960805-47
Beattie, Christine (Deceased)
Email: beattie.24@osu.edu, Christine.Beattie@osumc.edu
URL: http://u.osu.edu/zebrafish
Affiliation: Beattie Lab
Address: The Center for Molecular Neurobiology Department of Neuroscience The Ohio State University 190 Rightmire Hall 1060 Carmack Road Columbus, OH 43210 USA
Country: United States
Phone: (614) 292-5113
Fax: (614) 292-5379

   Our goal is to understand motoneuron development and function in the context of motoneuron diseases. We focus on two diseases, spinal muscular atrophy (SMA), an infant/childhood onset motoneuron disease and amyotrophic lateral sclerosis (ALS) and adult onset disease. We use zebrafish as a vertebrate model organism due to its well characterized nervous system and its relatively simple neuromuscular organization. We have generated genetic models of these diseases in zebrafish and are applying genetics, cell biology and electrophysiology to understand differences between wild-type motoneurons and motoneurons in these disease models.

SMA is an infant/childhood onset motoneuron disease. We have found that when the protein linked to this disease, survival motor neuron protein (SMN), is decreased motoneurons exhibit aberrant axonal development, decreased axonal actin dynamics, and decreased dendrites. Our goal now is to identify why this is and what genes downstream of SMN are involved. This will lend insight into the normal processes of motoneuron development and the function of this disease gene in the process.

ALS is an adult onset disease. However, we are very interested in understanding the earliest changes that occur in motoneurons in this disease. Our hypothesis is that changes occur early in the spinal cord and that over time these changes damage the cell to the point where it cannot function. We will test this hypothesis using a combination of electrophysiology, RNA expression analysis and in vivo calcium imaging. Knowledge of these early changes will not only define a mechanism of toxicity but will reveal in vivo biomarkers. In future work, these biomarkers can be used to design high throughput screens in zebrafish larvae to aid in drug development and testing.

Xu, J., Wu, P.J., Lai, T.H., Sharma, P., Canella, A., Welker, A.M., Beattie, C., Timmers, C.D., Lang, F.F., Jacob, N.K., Elder, J.B., Lonser, R., Easley, M., Pietrzak, M., Sampath, D., Puduvalli, V.K. (2022) Disruption of DNA Repair and Survival Pathways through Heat Shock Protein inhibition by Onalespib to Sensitize Malignant Gliomas to Chemoradiation therapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 28(9):1979-1990
Riboldi, G.M., Faravelli, I., Kuwajima, T., Delestrée, N., Dermentzaki, G., De Planell-Saguer, M., Rinchetti, P., Hao, L.T., Beattie, C.C., Corti, S., Przedborski, S., Mentis, G.Z., Lotti, F. (2021) Sumoylation regulates the assembly and activity of the SMN complex. Nature communications. 12:5040
Cam, M., Charan, M., Welker, A.M., Dravid, P., Studebaker, A.W., Leonard, J.R., Pierson, C.R., Nakano, I., Beattie, C.E., Hwang, E.I., Kambhampati, M., Nazarian, J., Finlay, J.L., Cam, H. (2019) ΔNp73/ETS2 complex drives glioblastoma pathogenesis- targeting downstream mediators by rebastinib prolongs survival in preclinical models of glioblastoma. Neuro-Oncology. 22(3):345-356
Banasavadi-Siddegowda, Y.K., Welker, A.M., An, M., Yang, X., Zhou, W., Shi, G., Imitola, J., Li, C., Hsu, S., Wang, J., Phelps, M., Zhang, J., Beattie, C.E., Baiocchi, R., Kaur, B. (2017) PRMT5 as a druggable target for glioblastoma therapy. Neuro-Oncology. 20(6):753-763
Hao, L.T., Duy, P.Q., An, M., Talbot, J., Iyer, C.C., Wolman, M., Beattie, C.E. (2017) HuD and the Survival Motor Neuron protein interact in motoneurons and are essential for motoneuron development, function and mRNA regulation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 37(48):11559-11571
Canella, A., Welker, A.M., Yoo, J.Y., Xu, J., Abbas, F.S., Kesanakurti, D., Nagarajan, P., Beattie, C.E., Sulman, E.P., Liu, J.L., Gumin, J., Lang, F.F., Gurcan, M., Kaur, B., Sampath, D., Puduvalli, V.K. (2017) Efficacy of Onalespib a Long-acting Second Generation HSP90 Inhibitor as a Single Agent and in Combination with Temozolomide Against Malignant Gliomas. Clinical cancer research : an official journal of the American Association for Cancer Research. 23(20):6215-6226
Welker, A.M., Jaros, B.D., An, M., Beattie, C.E. (2017) Changes in tumor cell heterogeneity after chemotherapy treatment in a xenograft model of glioblastoma. Neuroscience. 356:35-43
Duy, P.Q., Berberoglu, M.A., Beattie, C.E., Hall, C.W. (2017) Cellular responses to recurrent pentylenetetrazole-induced seizures in the adult zebrafish brain. Neuroscience. 349:118-127
Pan, C.C., Shah, N., Kumar, S., Wheeler, S.E., Cinti, J., Hoyt, D.G., Beattie, C.E., An, M., Mythreye, K., Rakotondraibe, L.H., Lee, N.Y. (2017) Angiostatic actions of capsicodendrin through selective inhibition of VEGFR2-mediated AKT signaling and disregulated autophagy. Oncotarget. 8(8):12675-12685
Welker, A.M., Jaros, B.D., Puduvalli, V.K., Imitola, J., Kaur, B., Beattie, C.E. (2016) Correction: Standardized orthotopic xenografts in zebrafish reveal glioma cell-line-specific characteristics and tumor cell heterogeneity. Disease models & mechanisms. 9:1063-5
Welker, A.M., Jaros, B.D., Puduvalli, V.K., Imitola, J., Kaur, B., Beattie, C.E. (2016) Standardized orthotopic xenografts in zebrafish reveal glioma cell line specific characteristics and tumor cell heterogeneity. Disease models & mechanisms. 9(2):199-210
Li, H., Custer, S.K., Gilson, T., Hao, L.T., Beattie, C.E., Androphy, E.J. (2015) α-COP binding to the survival motor neuron protein SMN is required for neuronal process outgrowth. Human molecular genetics. 24(25):7295-307
Martin, B.L., Gallagher, T.L., Rastogi, N., Davis, J.P., Beattie, C.E., Amacher, S.L., Janssen, P.M. (2015) In vivo assessment of contractile strength distinguishes differential gene function in skeletal muscle of zebrafish larvae. Journal of applied physiology (Bethesda, Md. : 1985). 119(7):799-806
McGovern, V.L., Massoni-Laporte, A., Wang, X., Le, T.T., Le, H.T., Beattie, C.E., Rich, M.M., Burghes, A.H. (2015) Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity in the ∆7 SMA Mouse. PLoS One. 10:e0132364
Hao, L.T., Phan, D.Q., Jontes, J.D., Beattie, C.E. (2015) Motoneuron development influences dorsal root ganglia survival and Schwann cell development in a vertebrate model of spinal muscular atrophy. Human molecular genetics. 24(2):346-60
Wiley, D.J., Juan, I., Le, H., Cai, X., Baumbach, L., Beattie, C., D'Urso, G. (2014) Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases. F1000Research. 3:121
Lyon, A.N., Pineda, R.H., Hao, L.T., Kudryashova, E., Kudryashov, D.S., and Beattie, C.E. (2014) Calcium binding is essential for plastin 3 function in Smn-deficient motoneurons. Human molecular genetics. 23(8):1990-2004
Biswas, S., Duy, P.Q., Hao le, T., Beattie, C.E., and Jontes, J.D. (2014) Protocadherin-18b interacts with Nap1 to control motor axon growth and arborization in zebrafish. Molecular biology of the cell. 25(5):633-42
Gassman, A., Hao le, T., Bhoite, L., Bradford, C.L., Chien, C.B., Beattie, C.E, and Manfredi, J.P. (2013) Small molecule suppressors of Drosophila Kinesin deficiency rescue motor axon development in a zebrafish model of spinal muscular atrophy. PLoS One. 8(9):e74325
Hao, L.T., Duy, P.Q., Jontes, J.D., Wolman, M., Granato, M., and Beattie, C.E. (2013) Temporal requirement for SMN in motoneuron development. Human molecular genetics. 22(13):2612-25
Pineda, R., Beattie, C.E., and Hall, C.W. (2013) Closed loop neural stimulation for pentylenetetrazole seizures in zebrafish. Disease models & mechanisms. 6(1):64-71
Lotti, F., Imlach, W.L., Saieva, L., Beck, E.S., Hao le, T., Li, D.K., Jiao, W., Mentis, G.Z., Beattie, C.E., McCabe, B.D., and Pellizzoni, L. (2012) An SMN-Dependent U12 Splicing Event Essential for Motor Circuit Function. Cell. 151(2):440-454
Hao, L.T., Wolman, M., Granato, M., and Beattie, C.E. (2012) Survival motor neuron affects plastin 3 protein levels leading to motor defects. The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(15):5074-5084
Dalgin, G., Ward, A.B., Hao le, T., Beattie, C.E., Nechiporuk, A., and Prince, V.E. (2011) Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas. Development (Cambridge, England). 138(21):4597-4608
Pineda, R., Beattie, C.E., and Hall, C.W. (2011) Recording the adult zebrafish cerebral field potential during pentylenetetrazole seizures. Journal of Neuroscience Methods. 200(1):20-8
Akten, B., Kye, M.J., Hao, L.T., Wertz, M.H., Singh, S., Nie, D., Huang, J., Merianda, T.T., Twiss, J.L., Beattie, C.E., Steen, J.A., and Sahin, M. (2011) Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits. Proceedings of the National Academy of Sciences of the United States of America. 108(25):10337-42
Hilario, J.D., Wang, C., and Beattie, C.E. (2010) Collagen XIXa1 is crucial for motor axon navigation at intermediate targets. Development (Cambridge, England). 137(24):4261-4269
Ramesh, T., Lyon, A.N., Pineda, R.H., Wang, C., Janssen, P.M., Canan, B.D., Burghes, A.H., and Beattie, C.E. (2010) A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease. Disease models & mechanisms. 3(9-10):652-662
Boon, K.L., Xiao, S., McWhorter, M.L., Donn, T., Wolf-Saxon, E., Bohnsack, M.T., Moens, C.B., and Beattie, C.E. (2009) Zebrafish survival motor neuron Mutants Exhibit Presynaptic Neuromuscular Junction Defects. Human molecular genetics. 18(19):3615-3625
Ackerman, K.M., Nakkula, R., Zirger, J.M., Beattie, C.E., and Boyd, R.T. (2009) Cloning and spatiotemporal expression of zebrafish neuronal nicotinic acetylcholine receptor alpha 6 and alpha 4 subunit RNAs. Developmental Dynamics : an official publication of the American Association of Anatomists. 238(4):980-992
Hilario, J., Rodino-Klapac, L.R., Wang, C., and Beattie, C.E. (2009) Semaphorin 5A is a bifunctional axon guidance cue for axial motoneurons in vivo. Developmental Biology. 326(1):190-200
McGovern, V.L., Gavrilina, T.O., Beattie, C.E., and Burghes, A.H. (2008) Embryonic motor axon development in the severe SMA mouse. Human molecular genetics. 17(18):2900-2909
Oprea, G.E., Kröber, S., McWhorter, M.L., Rossoll, W., Müller, S., Krawczak, M., Bassell, G.J., Beattie, C.E., and Wirth, B. (2008) Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science (New York, N.Y.). 320(5875):524-527
McWhorter, M.L., Boon, K.L., Horan, E.S., Burghes, A.H., and Beattie, C.E. (2008) The SMN binding protein gemin2 is not involved in motor axon outgrowth. Developmental Neurobiology. 68(2):182-194
Beattie, C.E., Carrel, T.L., and McWhorter, M.L. (2007) Fishing for a mechanism: using zebrafish to understand spinal muscular atrophy. Journal of Child Neurology. 22(8):995-1003
Carrel, T.L., McWhorter, M.L., Workman, E., Zhang, H., Wolstencroft, E.C., Lorson, C., Bassell, G.J., Burghes, A.H., and Beattie, C.E. (2006) Survival motor neuron function in motor axons is independent of functions required for small nuclear ribonucleoprotein biogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(43):11014-11022
Challa, A.K., McWhorter, M.L., Wang, C., Seeger, M.A., and Beattie, C.E. (2005) Robo3 isoforms have distinct roles during zebrafish development. Mechanisms of Development. 122(10):1073-1086
Rodino-Klapac, L.R., and Beattie, C.E. (2004) Zebrafish topped is required for ventral motor axon guidance. Developmental Biology. 273(2):308-320
Zirger, J.M., Beattie, C.E., McKay, D.B., and Thomas Boyd, R. (2003) Cloning and expression of zebrafish neuronal nicotinic acetylcholine receptors. Gene expression patterns : GEP. 3(6):747-754
Liu, K.S., Gray, M., Otto, S.J., Fetcho, J.R., and Beattie, C.E. (2003) Mutations in deadly seven/notch1a reveal developmental plasticity in the escape response circuit. The Journal of neuroscience : the official journal of the Society for Neuroscience. 23(22):8159-8166
McWhorter, M.L., Monani, U.R., Burghes, A.H., and Beattie, C.E. (2003) Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding. The Journal of cell biology. 162(5):919-932
Beattie, C.E., Granato, M., and Kuwada, J.Y. (2002) Cellular, genetic and molecular mechanisms of axonal guidance in the zebrafish. Results and problems in cell differentiation. 40:252-269
Gray, M., Moens, C.B., Amacher, S.L., Eisen, J.S., and Beattie, C.E. (2001) Zebrafish deadly seven functions in neurogenesis. Developmental Biology. 237(2):306-323
Shepherd, I.T., Beattie, C.E., and Raible, D.W. (2001) Functional analysis of zebrafish GDNF. Developmental Biology. 231(2):420-435
Challa, A.K., Beattie, C.E., and Seeger, M.A. (2001) Identification and characterization of roundabout orthologs in zebrafish. Mechanisms of Development. 101:243-247
Beattie, C.E. (2000) Control of motor axon guidance in the zebrafish embryo. Brain research bulletin. 53(5):489-500
Beattie, C.E., Melancon, E., and Eisen, J.S. (2000) Mutations in the stumpy gene reveal intermediate targets for zebrafish motor axons. Development (Cambridge, England). 127(12):2653-2662
Beattie, C.E., Raible, D.W., Henion, P.D., and Eisen, J.S. (1999) Early pressure screens. In The Zebrafish: Genetics and Genomics, H.W. Detrich, III, M. Westerfield, and L.I. Zon, eds., San Diego, CA: Academic Press, Methods Cell Biol.. 60:71-86
Beattie, C.E., Hatta, K., Halpern, M.E., Liu, H., Eisen, J.S., and Kimmel, C.B. (1997) Temporal separation in the specification of primary and secondary motoneurons in zebrafish. Developmental Biology. 187(2):171-182
Beattie, C.E. and Eisen, J.S. (1997) Notochord alters the permissiveness of myotome for pathfinding by an identified motoneuron in embryonic zebrafish. Development (Cambridge, England). 124(3):713-720
Henion, P.D., Raible, D.W., Beattie, C.E., Stoesser, K.L., Weston, J.A., and Eisen, J.S. (1996) Screen for mutations affecting development of zebrafish neural crest. Developmental genetics. 18:11-17