ZFIN ID: ZDB-LAB-000809-1
Jau-Nian Chen Lab
PI/Director: Chen, Jau-Nian
Contact Person: Chen, Jau-Nian
Email: chenjn@mcdb.ucla.edu
URL: http://www.mcdb.ucla.edu/Research/jnchen/Welcome.html
Address: Department of Molecular, Cell and Developmental Biology University of California, Los Angeles 621 Charles E. Young Drive, South Life Sciences Building, Room 5109 Los Angeles, CA 90095 USA
Country: United States
Phone: (310) 206-4512
Fax: (310) 206-3987
Line Designation: la

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Our laboratory is investigating the development of the cardiovascular system in zebrafish. We are employing both genetic and molecular approaches to identify genes that are responsible for cell-fate determination, proliferation and differentiation of cardiovascular precursors, and the patterning of the heart and vessels.

Several unique features make zebrafish ideal for genetic and embryological studies. For instance, the transparent nature of zebrafish embryos provides easy access to observe and study organ development in live embryos. About 100 mutations affecting cardiovascular development in zebrafish have already been identified in previous genetic screens. We are currently focusing on mutations affecting the size of the heart, the patterning of cardiac chambers and vessels. We are also doing positional cloning to identify genes that areresponsible for these phenotypes.

In addition we are generating transgenic zebrafish lines in which cardiac or vascular progenitor cells are markedby the expression of Green Fluorescent Protein (GFP). We will use these transgenic fish to conduct genetic screens to identify new mutations affecting cardiovascular development. We will also take a molecular approach by using these transgenic lines to identify genes controlling cell-fate determination and/or differentiation through microarray technology.

Choi, Jayoung Graduate Student Langenbacher, Adam Graduate Student Nguyen, Catherine Graduate Student
Dong, Linda Research Staff Huang, Jie Research Staff Langerman, Justin Research Staff

Shimizu, H., Huber, S., Langenbacher, A.D., Crisman, L., Huang, J., Wang, K., Wilting, F., Gudermann, T., Schredelseker, J., Chen, J.N. (2021) Glutamate 73 Promotes Anti-arrhythmic Effects of Voltage-Dependent Anion Channel Through Regulation of Mitochondrial Ca2+ Uptake. Frontiers in Physiology. 12:724828
Langenbacher, A.D., Shimizu, H., Hsu, W., Zhao, Y., Borges, A., Koehler, C., Chen, J.N. (2020) Mitochondrial Calcium Uniporter Deficiency in Zebrafish Causes Cardiomyopathy With Arrhythmia. Frontiers in Physiology. 11:617492
Ziyad, S., Riordan, J.D., Cavanaugh, A.M., Su, T., Hernandez, G.E., Hilfenhaus, G., Morselli, M., Huynh, K., Wang, K., Chen, J.N., Dupuy, A.J., Iruela-Arispe, M.L. (2018) A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis. Cell Reports. 22:1211-1224
Shimizu, H., Langenbacher, A.D., Huang, J., Wang, K., Otto, G., Geisler, R., Wang, Y., Chen, J.N. (2017) The Calcineurin-FoxO-MuRF1 signaling pathway regulates myofibril integrity in cardiomyocytes. eLIFE. 6
Lu, F., Langenbacher, A., Chen, J.N. (2017) Tbx20 drives cardiac progenitor formation and cardiomyocyte proliferation in zebrafish. Developmental Biology. 421(2):139-148
Berchtold, M.W., Zacharias, T., Kulej, K., Wang, K., Torggler, R., Jespersen, T., Chen, J.N., Larsen, M.R., La Cour, J.M. (2016) The Arrhythmogenic Calmodulin Mutation D129G Dysregulates Cell Growth, Calmodulin-dependent Kinase II Activity and Cardiac Function in Zebrafish. The Journal of biological chemistry. 291(52):26636-26646
Lu, F., Langenbacher, A.D., Chen, J.N. (2016) Transcriptional Regulation of Heart Development in Zebrafish. Journal of cardiovascular development and disease. 3(2)
Gao, C., Ren, S., Lee, J.H., Qiu, J., Chapski, D.J., Rau, C.D., Zhou, Y., Abdellatif, M., Nakano, A., Vondriska, T.M., Xiao, X., Fu, X.D., Chen, J.N., Wang, Y. (2016) RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure. The Journal of Clinical Investigation. 126(1):195-206
Cavanaugh, A.M., Huang, J., Chen, J.N. (2015) Two developmentally distinct populations of neural crest cells contribute to the zebrafish heart. Developmental Biology. 404(2):103-12
Shimizu, H., Schredelseker, J., Huang, J., Lu, K., Naghdi, S., Lu, F., Franklin, S., Fiji, H.D., Wang, K., Zhu, H., Tian, C., Lin, B., Nakano, H., Ehrlich, A., Nakai, J., Stieg, A.Z., Gimzewski, J.K., Nakano, A., Goldhaber, J.I., Vondriska, T.M., Hajnóczky, G., Kwon, O., Chen, J.N. (2015) Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity. eLIFE. 4:253-65
Lin, C., Yao, E., Wang, K., Nozawa, Y., Shimizu, H., Johnson, J.R., Chen, J.N., Krogan, N.J., Chuang, P.T. (2014) Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling. Genes & Development. 28:2547-63
Zhang, Y., Shimizu, H., Siu, K.L., Mahajan, A., Chen, J.N., Cai, H. (2014) NADPH Oxidase 4 Induces Cardiac Arrhythmic Phenotype in Zebrafish. The Journal of biological chemistry. 289(33):23200-8
Schredelseker, J., Paz, A., López, C.J., Altenbach, C., Leung, C.S., Drexler, M.K., Chen, J.N., Hubbell, W.L., Abramson, J. (2014) High Resolution Structure and Double Electron-Electron Resonance of the Zebrafish Voltage-dependent Anion Channel 2 Reveal an Oligomeric Population. The Journal of biological chemistry. 289:12566-77
Monte, E., Mouillesseaux, K., Chen, H., Kimball, T., Ren, S., Wang, Y., Chen, J.N., Vondriska, T.M., and Franklin, S. (2013) Systems Proteomics of Cardiac Chromatin Identifies Nucleolin as a Regulator of Growth and Cellular Plasticity in Cardiomyocytes. American journal of physiology. Heart and circulatory physiology. 305(11):H1624-38
Foster, W.H., Langenbacher, A., Gao, C., Chen, J., and Wang, Y. (2013) Nuclear phosphatase PPM1G in cellular survival and neural development. Developmental dynamics : an official publication of the American Association of Anatomists. 242(9):1101-9
Langenbacher, A.D., Huang, J., Chen, Y., and Chen, J.N. (2012) Sodium pump activity in the yolk syncytial layer regulates zebrafish heart tube morphogenesis. Developmental Biology. 362(2):263-270
Langenbacher, A.D., Nguyen, C.T., Cavanaugh, A.M., Huang, J., Lu, F., and Chen, J.N. (2011) The PAF1 complex differentially regulates cardiomyocyte specification. Developmental Biology. 353(1):19-28
Choi, J., Mouillesseaux, K., Wang, Z., Fiji, H.D., Kinderman, S.S., Otto, G.W., Geisler, R., Kwon, O., and Chen, J.N. (2011) Aplexone targets the HMG-CoA reductase pathway and differentially regulates arteriovenous angiogenesis. Development (Cambridge, England). 138(6):1173-1181
Mouillesseaux, K., and Chen, J.N. (2011) Mutation in utp15 Disrupts Vascular Patterning in a p53-Dependent Manner in Zebrafish Embryos. PLoS One. 6(9):e25013
Yu, F., Huang, J., Adlerz, K., Jadvar, H., Hamdan, M.H., Chi, N., Chen, J.N., and Hsiai, T.K. (2010) Evolving Cardiac Conduction Phenotypes in Developing Zebrafish Larvae: Implications to Drug Sensitivity. Zebrafish. 7(4):325-331
Nguyen, C.T., Langenbacher, A., Hsieh, M., and Chen, J.N. (2010) The Paf1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish. Developmental Biology. 341(1):167-175
Wilson, C.W., Nguyen, C.T., Chen, M.H., Yang, J.H., Gacayan, R., Huang, J., Chen, J.N., and Chuang, P.T. (2009) Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis. Nature. 459(7243):98-102
Colantonio, J.R., Vermot, J., Wu, D., Langenbacher, A.D., Fraser, S., Chen, J.N., and Hill, K.L. (2009) The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear. Nature. 457(7226):205-209
Nguyen, C.T. (2009) Genetic analysis of cardiac patterning in zebrafish. Ph.D. Thesis. :128p
Xie, Y., Ottolia, M., John, S., Chen, J.N., and Philipson, K.D. (2008) Conformational Changes of a Ca2+-Binding Domain of the Na+ -Ca2+ Exchanger Monitored by FRET in Transgenic Zebrafish Heart. American journal of physiology. Cell physiology. 295(2):C388-C393
Nguyen, C. T., Lu, Q., Wang, Y., Chen, J. (2008) Zebrafish as a model for cardiovascular development and disease. Drug Discovery Today: Disease Models. 5(3):135-140
Liu, J., Fraser, S.D., Faloon, P.W., Rollins, E.L., Vom Berg, J., Starovic-Subota, O., Laliberte, A.L., Chen, J.N., Serluca, F.C., and Childs, S.J. (2007) A βPix–Pak2a signaling pathway regulates cerebral vascular stability in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 104(35):13990-13995
Shu, X., Huang, J., Dong, Y., Choi, J., Langenbacher, A., and Chen, J.N. (2007) Na,K-ATPase α2 and Ncx4a regulate zebrafish left-right patterning. Development (Cambridge, England). 134(10):1921-1930
Choi, J., Dong, L., Ahn, J., Dao, D., Hammerschmidt, M., and Chen, J.N. (2007) FoxH1 negatively modulates flk1 gene expression and vascular formation in zebrafish. Developmental Biology. 304(2):735-744
Lu, G., Ren, S., Korge, P., Choi, J., Dong, Y., Weiss, J., Koehler, C., Chen, J.N, and Wang, Y. (2007) A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. Genes & Development. 21(7):784-796
Cibrian-Uhalte, E., Langenbacher, A., Shu, X., Chen, J.N., and Abdelilah-Seyfried, S. (2007) Involvement of zebrafish Na+,K+ ATPase in myocardial cell junction maintenance. The Journal of cell biology. 176(2):223-230
Mably, J.D., Chuang, L.P., Serluca, F.C., Mohideen, M.A., Chen, J.N., and Fishman, M.C. (2006) santa and valentine pattern concentric growth of cardiac myocardium in the zebrafish. Development (Cambridge, England). 133(16):3139-3146
Langenbacher, A.D., Dong, Y., Shu, X., Choi, J., Nicoll, D.A., Goldhaber, J.I., Philipson, K.D., and Chen, J.N. (2005) Mutation in sodium-calcium exchanger 1 (NCX1) causes cardiac fibrillation in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 102(49):17699-17704
Jin, S.W., Beis, D., Mitchell, T., Chen, J.N., Stainier, D.Y. (2005) Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development (Cambridge, England). 132(23):5199-5209
Beis, D., Bartman, T., Jin, S.W., Scott, I.C., D'Amico, L.A., Ober, E.A., Verkade, H., Frantsve, J., Field, H.A., Wehman, A., Baier, H., Tallafuss, A., Bally-Cuif, L., Chen, J.N., Stainier, D.Y., and Jungblut, B. (2005) Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development (Cambridge, England). 132(18):4193-4204
Huang, H., Zhang, B., Hartenstein, P.A., Chen, J.N., and Lin, S. (2005) NXT2 is required for embryonic heart development in zebrafish. BMC Developmental Biology. 5(1):7
Mably, J.D., Mohideen, M.A.P.K., Burns, C.G., Chen, J.-N., and Fishman, M.C. (2003) heart of glass regulates the concentric growth of the heart in zebrafish. Current biology : CB. 13(24):2138-2147
Shu, X., Cheng, K., Patel, N., Chen, F., Joseph, E., Tsai, H.-J., and Chen, J.-N. (2003) Na,K-ATPase is essential for embryonic heart development in the zebrafish. Development (Cambridge, England). 130:6165-6173
Cross, L.M., Cook, M.A., Lin, S., Chen, J.N., and Rubinstein, A.L. (2003) Rapid analysis of angiogenesis drugs in a live fluorescent zebrafish assay. Arterioscler. Thromb. Vasc. Biol.. 23(5):911-912
Childs, S., Chen, J.-N., Garrity, D.M., and Fishman, M.C. (2002) Patterning of angiogenesis in the zebrafish embryo. Development (Cambridge, England). 129(4):973-982
Peterson, R.T., Mably, J.D., Chen, J.-N., and Fishman, M.C. (2001) Convergence of distinct pathways to heart patterning reveals by the small molecule concentramide and the mutation heart-and-soul. Current biology : CB. 11:1481-1491
Chan, J., Mably, J.D., Serluca, F.C., Chen, J.-N., Goldstein, N.B., Thomas, M.C., Cleary, J.A., Brennan, C., Fishman, M.C., and Roberts, T.M. (2001) Morphogenesis of prechordal plate and notochord requires intact Eph/Ephrin B signaling. Developmental Biology. 234(2):470-482
Chen, J.-N., van Bebber, F., Goldstein, A.M., Serluca, F.C., Jackson, D., Childs, S., Serbedzija, G., Warren, K.S., Mably, J.D., Lindahl, P., Mayer, A., Haffter, P., and Fishman, M.C. (2001) Genetic steps to organ laterality in zebrafish. Comparative and functional genomics. 2(2):60-68
Chen, J.N. and Fishman, M.C. (2000) Genetics of heart development. Trends in genetics : TIG. 16(9):383-388
Park, M., Lewis, C., Turbay, D., Chung, A., Chen, J.-N., Evans, S., Breitbart, R.E., Fishman, M.C., Izumo, S., and Bodmer, R. (1998) Differential rescue of visceral and cardiac defects in Drosophila by vertebrate tinman-related genes. Proceedings of the National Academy of Sciences of the United States of America. 95(16):9366-9371
Serbedzija, G.N., Chen, J.-N., and Fishman, M.C. (1998) Regulation in the heart field of zebrafish. Development (Cambridge, England). 125:1095-1101
Chen, J.-N., van Eeden, F.J.M., Warren, K.S., Chin, A., Nüsslein-Volhard, C., Haffter, P., and Fishman, M.C. (1997) Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish. Development (Cambridge, England). 124(21):4373-4382
Chin, A.J., Chen, J.N., and Weinberg, E.S. (1997) Bone morphogenetic protein-4 expression characterizes inductive boundaries in organs of developing zebrafish. Development genes and evolution. 207(2):107-114
Chen, J.N. and Fishman, M.C. (1996) Zebrafish tinman homolog demarcates the heart field and initiates myocardial differentiation. Development (Cambridge, England). 122(12):3809-3816
Chen, J.N., Haffter, P., Odenthal, J., Vogelsang, E., Brand, M., van Eeden, F.J., Furutani-Seiki, M., Granato, M., Hammerschmidt, M., Heisenberg, C.P., Jiang, Y.J., Kane, D.A., Kelsh, R.N., Mullins, M.C., and Nüsslein-Volhard, C. (1996) Mutations affecting the cardiovascular system and other internal organs in zebrafish. Development (Cambridge, England). 123:293-302
Stainier, D.Y., Fouquet, B., Chen, J.N., Warren, K.S., Weinstein, B.M., Meiler, S.E., Mohideen, M.A., Neuhauss, S.C., Solnica-Krezel, L., Schier, A.F., Zwartkruis, F., Stemple, D.L., Malicki, J., Driever, W., and Fishman, M.C. (1996) Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo. Development (Cambridge, England). 123:285-292