ZFIN ID: ZDB-PERS-960805-115
Chung, Bon-chu
Email: mbchung@sinica.edu.tw
URL: http://www.imb.sinica.edu.tw/chung/
Affiliation: Chung Lab
Address: Institute of Molecular Biology Academia Sinica Nankang, Taipei, Taiwan
Country: Taiwan
Phone: 886-2-2789-9215
Fax: 886-2-2788 3464


I. Steroid Function and Regulation

My lab has been working on steroid function and regulation. Recently we have established mouse models to study steroid deficiency. We used a gene-targeting technique to disrupt Cyp11a1, the first gene in steroid biosynthetic pathways. These Cyp11a1 null mice did not synthesize steroids. They died shortly after birth, but could be rescued by steroid injection, yet male mice were feminized with female external genitalia and under-developed male accessory sex organs. In addition, their adrenal and gonads accumulated lipid and gradually degenerated. This provides a good model for the study of steroid deficiency.

II. Zebrafish Development

We have cloned zebrafish genes which play important roles during development. Among them, sox9 is important probably for cartilage development and testis formation. We find the sox9 gene is duplicated in zebrafish. Sox9a and sox9b expression patterns differ, indicating their separate role during development.

We have also characterized the expression and functions of steroidogenic genes, such as cyp11a1, cyp19, and 3-beta-HSD in zebrafish. These genes are mostly duplicated, with one gene expressed in the gonads and brain of zebrafish, similar to the expression pattern of the mammalian steroidogenic genes. The other zebrafish steroidogenic genes are expressed in the yolk syncytial layer during early embryogenesis, indicating the roles of steroids at this stage.

Pregnenolone, the immediate product of Cyp11a1, functions in promoting embryonic cell migration. Pregnenolone does so by binding to and activating a microtubule plus-end-binding protein, CLIP-170, which can promote microtubule polymerization, thus increasing cell motility. Currently we are continuing to investigate the functions of various steroids in zebrafish embryos and their roles in human beings.

Pan, Y.J., Tong, S.K., Hsu, C.W., Weng, J.H., Chung, B.C. (2022) Zebrafish Establish Female Germ Cell Identity by Advancing Cell Proliferation and Meiosis. Frontiers in cell and developmental biology. 10:866267
Hsu, C.W., Pan, Y.J., Wang, Y.W., Tong, S.K., Chung, B.C. (2018) Changes in the morphology and gene expression of developing zebrafish gonads. General and comparative endocrinology. 265:154-159
Miller, W.L., Chung, B.C. (2016) The First Defect in Electron Transfer to Mitochondrial P450 Enzymes. Endocrinology. 157:1003-6
Lin, J.C., Hu, S., Ho, P.H., Hsu, H.J., Postlethwait, J., Chung, B.C. (2016) Corrigendum. Two zebrafish hsd3b genes are distinct in function, expression and evolution. Endocrinology. 157:978
Vignet, C., Joassard, L., Lyphout, L., Guionnet, T., Goubeau, M., Le Menach, K., Brion, F., Kah, O., Chung, B.C., Budzinski, H., Bégout, M.L., Cousin, X. (2015) Exposures of zebrafish through diet to three environmentally relevant mixtures of PAHs produce behavioral disruptions in unexposed F1 and F2 descendant. Environmental science and pollution research international. 22(21):16371-83
Lin, J.C., Hu, S., Ho, P.H., Hsu, H.J., Postlethwait, J., Chung, B.C. (2015) Two zebrafish hsd3b genes are distinct in function, expression and evolution. Endocrinology. 156(8):2854-62
Kuo, M.W., Lou, S.W., Chung, B.C. (2014) Hedgehog-PKA Signaling and gnrh3 Regulate the Development of Zebrafish gnrh3 Neurons. PLoS One. 9:e95545
Weng, J.H., Liang, M.R., Chen, C.H., Tong, S.K., Huang, T.C., Lee, S.P., Chen, Y.R., Chen, C.T., and Chung, B.C. (2013) Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration. Nature Chemical Biology. 9(10):636-42
Brion, F., Le Page, Y., Piccini, B., Cardoso, O., Tong, S.K., Chung, B.C., and Kah, O. (2012) Screening Estrogenic Activities of Chemicals or Mixtures In Vivo Using Transgenic (cyp19a1b-GFP) Zebrafish Embryos. PLoS One. 7(5):e36069
Vosges, M., Le Page, Y., Chung, B.C., Combarnous, Y., Porcher, J.M., Kah, O., and Brion, F. (2010) 17alpha-Ethinylestradiol disrupts the ontogeny of the forebrain GnRH system and the expression of brain aromatase during early development of zebrafish. Aquatic toxicology (Amsterdam, Netherlands). 99(4):479-491
Tong, S.K., Hsu, H.J., and Chung, B.C. (2010) Zebrafish monosex population reveals female dominance in sex determination and earliest events of gonad differentiation. Developmental Biology. 344(2):849-856
Hsu, H.J., Lin, J.C., and Chung, B.C. (2009) Zebrafish cyp11a1 and hsd3b Genes: Structure, Expression and Steroidogenic Development during Embryogenesis. Molecular and cellular biology. 312(1-2):31-34
Mouriec, K., Lareyre, J.J., Tong, S.K., Le Page, Y., Vaillant, C., Pellegrini, E., Pakdel, F., Chung, B.C., Kah, O., and Anglade, I. (2009) Early regulation of brain aromatase (cyp19a1b) by estrogen receptors during zebrafish development. Developmental dynamics : an official publication of the American Association of Anatomists. 238(10):2641-2651
Tong, S.K., Mouriec, K., Kuo, M.W., Pellegrini, E., Gueguen, M.M., Brion, F., Kah, O., and Chung, B.C. (2009) A cyp19a1b-gfp (aromatase B) transgenic zebrafish line that expresses GFP in radial glial cells. Genesis (New York, N.Y. : 2000). 47(2):67-73
Kah, O., Pellegrini, E., Mouriec, K., Diotel, N., Anglade, I., Vaillant, C., Thieulant, M.L., Tong, S.K., Brion, F., Chung, B.C., and Pakdel, F. (2009) Oestrogens and neurogenesis: new functions for an old hormone. Lessons from the zebrafish. Journal de la Societe de biologie. 203(1):29-38
Hsu, H.J., Hsu, N.C., Hu, M.C., and Chung, B.C. (2006) Steroidogenesis in zebrafish and mouse models. Molecular and Cellular Endocrinology. 248(1-2):160-163
Hsu, H.J., Liang, M.R., Chen, C.T., and Chung, B.C. (2006) Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement. Nature. 439(7075):480-483
Sheela, S.G., Lee, W.C., Lin, W.W., and Chung, B.C. (2005) Zebrafish ftz-f1a (nuclear receptor 5a2) functions in skeletal muscle organization. Developmental Biology. 286(2):377-390
Kuo, M.W., Postlethwait, J., Lee, W.C., Lou, S.W., Chan, W.K., and Chung, B.C. (2005) Gene duplication, gene loss and evolution of expression domains in the vertebrate nuclear receptor NR5A (Ftz-F1) family. The Biochemical journal. 389(Pt 1):19-26
Kuo, M.W., Lou, S.W., Postlethwait, J., and Chung, B.C. (2005) Chromosomal Organization, Evolutionary Relationship, and Expression of Zebrafish GnRH Family Members. Journal of Biomedical Science. 12(4):629-639
Hsu, H.J., Lin, G., and Chung, B.C. (2004) Parallel early development of zebrafish interrenal glands and pronephros: differential control by wt1 and ff1b. Endocrine research. 30(4):803
Hu, M.C., Hsu, H.J., Guo, I.C., and Chung, B.C. (2004) Function of Cyp11a1 in animal models. Molecular and Cellular Endocrinology. 215(1-2):95-100
Tong, S.K. and Chung, B. (2003) Analysis of zebrafish cyp19 promoters. Journal of steroid biochemistry. 86(3-5):381-386
Hsu, H.-J., Lin, G., and Chung, B.-C. (2003) Parallel early development of zebrafish interrenal glands and pronephros: differential control by wt1 and ff1b. Development (Cambridge, England). 130(10):2107-2116
Hsu, H.J., Hsiao, P., Kuo, M.W., and Chung, B.C. (2002) Expression of zebrafish cyp11a1 as a maternal transcript and in yolk syncytial layer. Gene expression patterns : GEP. 2(3-4):219-222
Yan, Y.-L., Miller, C.T., Nissen, R.M., Singer, A., Liu, D., Kirn, A., Draper, B., Willoughby, J., Morcos, P.A., Amsterdam, A., Chung, B.-C., Westerfield, M., Haffter, P., Hopkins, N., Kimmel, C., and Postlethwait, J.H. (2002) A zebrafish sox9 gene required for cartilage morphogenesis. Development (Cambridge, England). 129(21):5065-5079
Chiang, E.F.L., Yan, Y.L., Tong, S.K., Hsiao, P.H., Guiguen, Y., Postlethwait, J., and Chung, B.C. (2001) Characterization of duplicated zebrafish cyp19 genes. The Journal of experimental zoology. 290(7):709-714
Tong, S.K., Chiang, E.F., Hsiao, P.H., and Chung, B. (2001) Phylogeny, expression and enzyme activity of zebrafish cyp19 (P450 aromatase) genes. The Journal of steroid biochemistry and molecular biology. 79(1-5):299-303
Trant, J.M., Gavasso, S., Ackers, J., Chung, B.-C., and Place, A.R. (2001) Developmental expression of cytochrome P450 aromatase genes (CYP19a and CYP19b) in zebrafish fry (Danio rerio). The Journal of experimental zoology. 290(5):475-83
Chiang, E.F., Yan, Y.-L., Guiguen, Y., Postlethwait, J., and Chung, B.-C. (2001) Two Cyp19 (P450 aromatase) genes on duplicated zebrafish chromosomes are expressed in ovary or brain. Mol. Biol. Evol.. 18(4):542-550
Chiang, E., Pai, C.-I., Wyatt, M., Yan, Y-L., Postlethwait, J., and Chung, B.-C. (2001) Two sox9 genes on duplicated zebrafish chromosomes: expression of similar transcription activators in distinct sites. Developmental Biology. 229:149-163
Hu, M., Chiang, E.F., Tong, S., Lai, W., Hsu, N., Wang, L.C., and Chung, B. (2001) Regulation of steroidogenesis in transgenic mice and zebrafish. Molecular and Cellular Endocrinology. 171(1-2):9-14
Lin, W.W., Wang, H.W., Sum, C., Liu, D., Hew, C.L., and Chung, B.C. (2000) Zebrafish ftz-f1 gene has two promoters, is alternatively spliced, and is expressed in digestive organs. The Biochemical journal. 348(2):439-446
Lai, W.W.K., Hsiao, P.H., Guiguen, Y., and Chung, B.C. (1998) Cloning of zebrafish cDNA for 3ß-hydroxysteroid dehydrogenase and p450SCC. Endocrine research. 24:927-931

Wu D–A, Chung B–c, Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity respectively. J. Clin. Invest. 88, 519-523 (1991).

Chou S-J, Lai K-N, Chung B-c, Characterization of the upstream sequence of the human CYP11A1 gene for cell type-specific expression. J. Biol. Chem. 271, 22125-22129 (1996).

Hu M-C, Hsu N-C, Ben El Hadj N, Pai C-I, Chu H-P, Wang C-KL, Chung B-c, Steroid Deficiency Syndromes in Mice with a Targeted Disruption of Cyp11a1. Mol. Endocrinol. 16, 1943-1950 (2002).

Chen W-Y, Weng J-H, Huang, C-C, Chung B-c, Histone deacetylase inhibitors reduce steroidogenesis through SCF-mediated ubiquitination and degradation of Steroidogenic Factor 1 (NR5A1). Mol. Cell. Biol. 27, 7284-7290 (2007)

Wang C-Y, Kao Y-H, Lai P-Y, Chen W-Y, and Chung B-c, Steroidogenic Factor-1 (NR5A1) Maintains Centrosome Homeostasis in Steroidogenic Cells by Restricting Centrosomal DNA-PK Activation. Mol Cell Biol, 33, 476-484 (2013).

Huang S-C, Lee C-t, Chung B-c, Tumor Necrosis Factor Suppresses NR5A2 Activity and Intestinal Glucocorticoid Synthesis to Sustain Chronic Colitis. Sci Signal, 7 (314), ra20, 1-11 (2014).

Wang C-Y, Huang EY-H, Huang S-C, and Chung B-c, DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress. Oncogene, Mar 24. doi: 10.1038/onc.2014.74. (2014)