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系統識別號 U0026-0102201317262800
論文名稱(中文) Wnt蛋白質在小鼠毛髮不同發育階段的分布
論文名稱(英文) Wnt Proteins at Different Stages of Hair Development in Mice
校院名稱 成功大學
系所名稱(中) 生物科技研究所
系所名稱(英) Institute of Biotechnology
學年度 101
學期 1
出版年 102
研究生(中文) 蔡淯亘
研究生(英文) Yu-Hsuan Tsai
學號 l66994089
學位類別 碩士
語文別 中文
論文頁數 93頁
口試委員 指導教授-黃玲惠
召集委員-張中興
口試委員-許漢銘
口試委員-楊朝鈞
中文關鍵字 頭髮缺失  毛囊發育  Wnt蛋白質  免疫組織化學染色法  體外毛囊再生培養系統 
英文關鍵字 Alopecia  hair follicle development  Wnt proteins  immunohistochemistry  hair follicle in vitro culture system 
學科別分類
中文摘要 頭髮脫落是正常的生理現象,但當毛囊的生長週期失去平衡,便會有禿頭的情形產生,若頭髮缺失則容易使人們產生心理壓力,因此毛囊再生一直是再生醫學界想要達成的目標。影響及調控毛囊發育之因子有很多,像是環境因素或者與毛囊發育及生長週期相關的細胞或生長因子。而在許多研究中皆證實了Wnt蛋白質家族對於毛囊發育及毛髮生長是不可或缺的一項因素。因此本研究的目的是藉由免疫組織化學染色法,針對Wnt蛋白質在小鼠毛囊不同發育階段的分布與表現量做一系列的觀察與記錄,從結果發現參與在非傳統Wnt訊息傳遞路徑中的Wnt 5a、Wnt 7a及Wnt 11在胚胎第13.5天之未分化的表皮中皆有明顯表現,推測其可能參與在促使細胞開始分化的第一個真皮訊號之中。此外,在傳統Wnt/β-catenin訊息傳遞路徑中,也發現Wnt 10b和β-catenin在各個發育階段中的表現有相呼應的情形。期望本研究的結果能作為他人將來建立體外毛囊再生培養系統模型之依據,也希望能因而更進一步瞭解毛囊的生物特性,並發展出有效率的毛囊再生方法。
英文摘要 Hair loss is a normal physiological phenomenon. Once the hair follicle growth cycle loss its balance, it may bring about alopecia. It is easy to make people feeling psychological stress. Therefore, regeneration of hair follicle has been the purpose that regeneration medical professions want to resolve. There are many factors would regulate the hair follicle development, such as environmental factors, development of hair follicle and hair cycle associated cells or growth factors all have effects on hair follicle development and hair growth. Many studies have shown that Wnt proteins are essential factors in hair follicle development and hair growth. So the purpose of this study is using the immunohistochemistry to observe the distribution and expression level at different developmental stages in mice. According to the results, Wnt 5a, Wnt 7a and Wnt 11, as the non-canonical Wnts, they are expressed in the undifferentiated epidermis at E13.5. Therefore, we presume that they might participate in the first dermal signal to promote cells to differentiate. Besides, we also found that Wnt 10b and β-catenin, as the canonical Wnts, have the similar expression at different developmental stages of hair follicle. To expect that this study can not only act as a basis for constructing the hair follicle regeneration in vitro culture system, but also hope to understand the biological characteristics of hair follicle much more and develop another efficient method for regeneration of hair follicle.
論文目次 中文摘要 1
Abstract 2
誌謝 3
目錄 5
表目錄 7
圖目錄 8
第一章 研究背景與目的 9
1.1 毛囊之簡介 9
1.1.1 毛囊之結構 10
1.1.2 毛囊之發育與形態發生 11
1.1.3 毛髮之生長週期(hair cycle) 15
1.1.3.1 生長期(Anagen) 15
1.1.3.2 退化期(Catagen) 15
1.1.3.3 休止期(Telogen) 16
1.2 影響及調控毛囊發育與毛髮生長週期之因子 16
1.2.1 Wnt蛋白質 18
1.2.1.1 Wnt蛋白質之種類 19
1.2.1.2 Wnt蛋白質相關之訊息傳遞 19
1.2.2 骨形態發生蛋白(Bone morphogenetic protein, BMPs) 21
1.3 實驗目的 22
1.4 實驗設計 23
1.4.2 Wnt蛋白質的分布 23
1.4.3 Wnt蛋白質的分布及表現程度之統計 24
第二章 研究材料與方法 25
2.1 藥品與試劑 25
2.2 抗體 26
2.3 儀器設備 26
2.4 方法 27
2.4.1 實驗動物檢體之選擇及收集 27
2.4.1.1 實驗動物檢體之選擇 27
2.4.1.2 實驗動物檢體之收集 28
2.4.2 Wnt蛋白質的分布 28
2.4.2.1 組織之石蠟包埋及切片 28
2.4.2.2 蘇木素-伊紅染色(H&E staining) 28
2.4.2.3 免疫組織化學染色法(Immunohistochemistry) 29
2.4.3 Wnt蛋白質的分布及表現程度之統計 32
第三章 實驗結果與討論 33
3.1 實驗動物檢體之收集 33
3.2 Wnt蛋白質的分布及表現程度 33
3.2.1 控制組 33
3.2.2 傳統Wnt/β-catenin訊息傳遞路徑 34
3.2.3 非傳統Wnt訊息傳遞路徑 39
3.3 討論 41
第四章 參考資料 46
第五章 附錄 50
參考文獻 1. Araújo, R., et al., Biology of Human Hair: Know Your Hair to Control It. 2010. 125: p. 121-143.
2. Hirsinger, E., et al., Role of growth factors in shaping the developing somite. Mol Cell Endocrinol, 1998. 140(1-2): p. 83-7.
3. Morasso, M.I. and M. Tomic-Canic, Epidermal stem cells: the cradle of epidermal determination, differentiation and wound healing. Biol Cell, 2005. 97(3): p. 173-83.
4. Millar, S.E., Molecular mechanisms regulating hair follicle development. The Journal of investigative dermatology, 2002. 118(2): p. 216-25.
5. Schmidt-Ullrich, R. and R. Paus, Molecular principles of hair follicle induction and morphogenesis. Bioessays, 2005. 27(3): p. 247-61.
6. Alonso, L. and E. Fuchs, The hair cycle. J Cell Sci, 2006. 119(Pt 3): p. 391-3.
7. Fernandes, K.J., et al., A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol, 2004. 6(11): p. 1082-93.
8. Stenn, K.S. and R. Paus, Controls of hair follicle cycling. Physiol Rev, 2001. 81(1): p. 449-494.
9. Yu, B.D., A. Mukhopadhyay, and C. Wong, Skin and hair: models for exploring organ regeneration. Human Molecular Genetics, 2008. 17(R1): p. R54-R59.
10. Nusse, R. and H.E. Varmus, Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982. 31(1): p. 99-109.
11. Ling, L., V. Nurcombe, and S.M. Cool, Wnt signaling controls the fate of mesenchymal stem cells. Gene, 2009. 433(1-2): p. 1-7.
12. Clevers, H., Wnt/β-Catenin Signaling in Development and Disease. Cell, 2006. 127(3): p. 469-480.
13. Wodarz, A. and R. Nusse, Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol, 1998. 14: p. 59-88.
14. Miller, J.R., The Wnts. Genome Biol, 2002. 3(1): p. REVIEWS3001.
15. Huelsken, J. and W. Birchmeier, New aspects of Wnt signaling pathways in higher vertebrates. Curr Opin Genet Dev, 2001. 11(5): p. 547-53.
16. Huelsken, J. and J. Behrens, The Wnt signalling pathway. J Cell Sci, 2002. 115(Pt 21): p. 3977-8.
17. Gordon, M.D., Wnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors. Journal of Biological Chemistry, 2006. 281(32): p. 22429-22433.
18. DasGupta, R. and E. Fuchs, Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development, 1999. 126(20): p. 4557-68.
19. Chu, E.Y., et al., Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development, 2004. 131(19): p. 4819-29.
20. Huelsken, J., et al., beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell, 2001. 105(4): p. 533-45.
21. Botchkarev, V.A., et al., Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nat Cell Biol, 1999. 1(3): p. 158-64.
22. Li, X., et al., Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem, 2005. 280(20): p. 19883-7.
23. Mao, B., et al., Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature, 2002. 417(6889): p. 664-7.
24. Petiot, A., et al., A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning. Development, 2003. 130(22): p. 5493-501.
25. Uyttendaele, H., et al., Activation of Notch1 in the hair follicle leads to cell-fate switch and Mohawk alopecia. Differentiation, 2004. 72(8): p. 396-409.
26. Zhou, P., et al., Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. Genes Dev, 1995. 9(6): p. 700-13.
27. Merrill, B.J., et al., Tcf3: a transcriptional regulator of axis induction in the early embryo. Development, 2004. 131(2): p. 263-74.
28. Zhang, Y., et al., Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction. Dev Cell, 2009. 17(1): p. 49-61.
29. Andl, T., et al., WNT signals are required for the initiation of hair follicle development. Dev Cell, 2002. 2(5): p. 643-53.
30. Reddy, S., et al., Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mech Dev, 2001. 107(1-2): p. 69-82.
31. Roberts, D.M., K.C. Slep, and M. Peifer, It takes more than two to tango: Dishevelled polymerization and Wnt signaling. Nat Struct Mol Biol, 2007. 14(6): p. 463-5.
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