Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20216
標題: Hedgehog pathway在雞的配子發育中所扮演的角色
The role of Hedgehog pathway in chicken gametogenesis
作者: 林家貝
Lin, Chia-Pei
關鍵字: 雞;Hedgehog;配子;睪丸;卵巢;gamete;testis;ovary
出版社: 生命科學系所
引用: 1 Clinton, M. Sex determination and gonadal development: a bird''s eye view. The Journal of experimental zoology 281, 457-465 (1998). 2 Nakamura, M., Kuwana, T., Miyayama, Y. & Fujimoto, T. Extragonadal distribution of primordial germ cells in the early chick embryo. The Anatomical record 222, 90-94, doi:10.1002/ar.1092220113 (1988). 3 Carlon, N. & Stahl, A. Origin of the somatic components in chick embryonic gonads. Archives d''anatomie microscopique et de morphologie experimentale 74, 52-59 (1985). 4 Smith, C. A. & Sinclair, A. H. Sex determination in the chicken embryo. The Journal of experimental zoology 290, 691-699 (2001). 5 Gilbert, S. F. Developmental Biology. 529-622 (Sinauer Associates USA, 2006). 6 Ahtiainen, M., Toppari, J., Poutanen, M. & Huhtaniemi, I. Indirect Sertoli cell-mediated ablation of germ cells in mice expressing the inhibin-alpha promoter/herpes simplex virus thymidine kinase transgene. Biol Reprod 71, 1545-1550, doi:10.1095/biolreprod.104.028183 (2004). 7 de Rooij, D. G. Stem cells in the testis. Int J Exp Pathol 79, 67-80 (1998). 8 Lin, M., Jones, R. C. & Blackshaw, A. W. The cycle of the seminiferous epithelium in the Japanese quail (Coturnix coturnix japonica) and estimation of its duration. Journal of reproduction and fertility 88, 481-490 (1990). 9 Lin, M. & Jones, R. C. Spatial arrangement of the stages of the cycle of the seminiferous epithelium in the Japanese quail, Coturnix coturnix japonica. Journal of reproduction and fertility 90, 361-367 (1990). 10 In Felig P, B. J., Broadus AE, et al. Endocrinology and Metabolism. (McGraw-Hill New York, 1995). 11 Erickson, G. F., Magoffin, D. A., Dyer, C. A. & Hofeditz, C. The ovarian androgen producing cells: a review of structure/function relationships. Endocrine reviews 6, 371-399 (1985). 12 Smith, C. A., Roeszler, K. N., Bowles, J., Koopman, P. & Sinclair, A. H. Onset of meiosis in the chicken embryo; evidence of a role for retinoic acid. BMC Dev Biol 8, 85, doi:10.1186/1471-213X-8-85 (2008). 13 Hardin, B. K. Principles of Cell Biology. (Pearson Education Inc., 2012). 14 Livera, G., Rouiller-Fabre, V., Valla, J. & Habert, R. Effects of retinoids on the meiosis in the fetal rat ovary in culture. Mol Cell Endocrinol 165, 225-231 (2000). 15 Li, H. & Clagett-Dame, M. Vitamin A deficiency blocks the initiation of meiosis of germ cells in the developing rat ovary in vivo. Biol Reprod 81, 996-1001, doi:10.1095/biolreprod.109.078808 (2009). 16 Huang, H. F. & Hembree, W. C. Spermatogenic response to vitamin A in vitamin A deficient rats. Biol Reprod 21, 891-904 (1979). 17 Sobhon, P., Mitranond, V., Tosukhowong, P. & Chindaduangrat, W. Cytological changes in the testes of vitamin-A-deficient rats. II. Ultrastructural study of the seminiferous tubules. Acta anatomica 103, 169-183 (1979). 18 van Pelt, A. M. & de Rooij, D. G. Synchronization of the seminiferous epithelium after vitamin A replacement in vitamin A-deficient mice. Biol Reprod 43, 363-367 (1990). 19 Griswold, M. D. et al. Function of vitamin A in normal and synchronized seminiferous tubules. Annals of the New York Academy of Sciences 564, 154-172 (1989). 20 Russell, M. C., Cowan, R. G., Harman, R. M., Walker, A. L. & Quirk, S. M. The hedgehog signaling pathway in the mouse ovary. Biol Reprod 77, 226-236, doi:10.1095/biolreprod.106.053629 (2007). 21 Yang, Y. et al. Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb. Development 124, 4393-4404 (1997). 22 Marti, E., Bumcrot, D. A., Takada, R. & McMahon, A. P. Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 375, 322-325, doi:10.1038/375322a0 (1995). 23 Porter, J. A. et al. Hedgehog patterning activity: Role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain. Cell 86, 21-34, doi:Doi 10.1016/S0092-8674(00)80074-4 (1996). 24 Pepinsky, R. B. et al. Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem 273, 14037-14045 (1998). 25 Chen, M. H., Wilson, C. W. & Chuang, P. T. SnapShot: hedgehog signaling pathway. Cell 130, 386, doi:10.1016/j.cell.2007.07.017 (2007). 26 Varjosalo, M. & Taipale, J. Hedgehog: functions and mechanisms. Genes Dev 22, 2454-2472, doi:10.1101/gad.1693608 (2008). 27 Bitgood, M. J., Shen, L. & McMahon, A. P. Sertoli cell signaling by Desert hedgehog regulates the male germline. Curr Biol 6, 298-304 (1996). 28 Yao, H. H. & Capel, B. Disruption of testis cords by cyclopamine or forskolin reveals independent cellular pathways in testis organogenesis. Dev Biol 246, 356-365, doi:10.1006/dbio.2002.0663 (2002). 29 Yao, H. H., Whoriskey, W. & Capel, B. Desert Hedgehog/Patched 1 signaling specifies fetal Leydig cell fate in testis organogenesis. Genes Dev 16, 1433-1440, doi:10.1101/gad.981202 (2002). 30 Hui-Ru, W. A study on Hedgehog pathway during male gonad development, Department of Life Sciences, National Chung Hsing University, Taiwan, (2008). 31 Jiun-Jie, C. The role of Sonic Hedgehog during chicken testis development, Department of Life Sciences, National Chung Hsing University, Taiwan, (2011). 32 Wijgerde, M., Ooms, M., Hoogerbrugge, J. W. & Grootegoed, J. A. Hedgehog signaling in mouse ovary: Indian hedgehog and desert hedgehog from granulosa cells induce target gene expression in developing theca cells. Endocrinology 146, 3558-3566, doi:10.1210/en.2005-0311 (2005). 33 Forbes, A. J., Lin, H., Ingham, P. W. & Spradling, A. C. hedgehog is required for the proliferation and specification of ovarian somatic cells prior to egg chamber formation in Drosophila. Development 122, 1125-1135 (1996). 34 Zhang, Y. & Kalderon, D. Hedgehog acts as a somatic stem cell factor in the Drosophila ovary. Nature 410, 599-604, doi:10.1038/35069099 (2001). 35 Ren, Y., Cowan, R. G., Harman, R. M. & Quirk, S. M. Dominant activation of the hedgehog signaling pathway in the ovary alters theca development and prevents ovulation. Mol Endocrinol 23, 711-723, doi:10.1210/me.2008-0391 (2009). 36 Migone, F. F. et al. Dominant activation of the hedgehog signaling pathway alters development of the female reproductive tract. Genesis 50, 28-40, doi:10.1002/dvg.20786 (2012). 37 Dwyer, J. R. et al. Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells. J Biol Chem 282, 8959-8968, doi:10.1074/jbc.M611741200 (2007). 38 Kim, S. K. & Melton, D. A. Pancreas development is promoted by cyclopamine, a hedgehog signaling inhibitor. Proc Natl Acad Sci U S A 95, 13036-13041 (1998). 39 Engel, B. D. et al. A cell-based screen for inhibitors of flagella-driven motility in Chlamydomonas reveals a novel modulator of ciliary length and retrograde actin flow. Cytoskeleton (Hoboken) 68, 188-203, doi:10.1002/cm.20504 (2011). 40 Firestone, A. J. et al. Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dynein. Nature 484, 125-129, doi:10.1038/nature10936 (2012). 41 Hyman, J. M. et al. Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. Proc Natl Acad Sci U S A 106, 14132-14137, doi:10.1073/pnas.0907134106 (2009).
摘要: 
在脊椎動物中,許多器官的發育皆受Hedgehog pathway所調控,而 Hedgehog的成員包括Dhh、Shh和Ihh。以缺失DHH的老鼠為例,無法發育成熟的精子因而導致不育;但雌性依然可以發育成熟的卵子。雌性的生殖細胞在胚胎時期即受RA誘導,開始進行減數分裂;而雄性則是進入發身期後才開始進行減數分裂。在實驗室成員過去的研究中發現,雞的Shh取代Dhh參與精子的發育,對成熟公雞給予外源性Shh後,將使同一截面中精子的形成週期同步化;若給予Cyclopamine則生殖細胞無法繼續發育。為進一步探討Shh在精子形成早期如何進行調控,我們對進入發身期前的公雞,提供RCAS-cShh或20(S)-Hydroxycholesterol,表現PTCH的細胞數目要到第八週才會提升;給予Ciliobrevin A可減少表現PTCH的細胞數目。但無論Hh的活性高低,表現NANOG的細胞數目不受Hh活性影響。顯示生殖幹細胞的數目並不會受Hh活性所影響。而在CAM culture的雌性胚胎卵巢中,給予20(S)-Hydroxycholesterol後表現PTCH的細胞數目增加,且有大量生殖細胞進入減數分裂;給予Cyclopamine後表現TCH的細胞數目減少,而生殖細胞的數目也會減少。因此,在第八週前活化Hh pathway並不會增加PTCH的表現量;生殖幹細胞的數目在發身期前不受到Hh之活性影響;抑制卵巢中Hh之活性將使卵子數目減少。

In vertebrate, Hedgehog pathway regulates the development of many organs, there are three members of the HH family: Dhh,Shh and Ihh. The Dhh-null mice are sterility in male owing to absence mature sperm but fertility in female. RA induces germ cells entry of meiosis in female embryonic stage, but not until puberty in male. Our past studies showed that Shh instead of Dhh regulates the development of testis in male chicken. In mature male chicken, ectopic Hh caused synchronous spermatogenesis progression but repressed spermatogenesis by Cyclopamine. To further understand how Hh pathway regulates spermatogenesis, we elevated HH pathway activity in prepubertal testis by providing RCAS-cShh / 20(S)-Hydroxycholesterol( Hh agonist). We found ectopic activating Hh pathway did NOT change the percentage of PTCH+ and NANOG+ cells in W7 testis, but 20(S)-Hydroxycholesterol increased the percentage of PTCH+ cells in W8 testis. Ciliobrevin A decreasing the percentage of PTCH+ cells but not NANOG+ cells. In cultured embryonic ovary, activateing Hh pathway increased the number of PTCH+ germ cells; while inhibiting Hh pathway not only inhibited Ptch expression, but also reduced germ cell number. Hence, ectopic Hh activation could NOT induce precocious spermatogenesis before W8 in testis. The spermatogonia stem cell number is NOT affected by either activation or inhibition of Hh pathway in prepubertal testis. Inhibition of Hh led to fewer germ cells in embryonic ovary.
URI: http://hdl.handle.net/11455/20216
其他識別: U0005-3008201311465500
Appears in Collections:生命科學系所

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.