Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 生化科學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73525
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor管永恕(Yung-Shu Kuan)
dc.contributor.authorShu-Heng Linen
dc.contributor.author林書恒zh_TW
dc.date.accessioned2021-06-17T07:39:57Z-
dc.date.available2024-02-19
dc.date.copyright2019-02-19
dc.date.issued2019
dc.date.submitted2019-02-15
dc.identifier.citationAmo, R., Aizawa, H., Takahoko, M., Kobayashi, M., Takahashi, R., Aoki, T., Okamoto, H., 2010. Identification of the zebrafish ventral habenula as a homolog of the mammalian lateral habenula. J Neurosci 30, 1566-1574.
Appelbaum, L., Wang, G.X., Maro, G.S., Mori, R., Tovin, A., Marin, W., Yokogawa, T., Kawakami, K., Smith, S.J., Gothilf, Y., Mignot, E., Mourrain, P., 2009. Sleep-wake regulation and hypocretin-melatonin interaction in zebrafish. Proceedings of the National Academy of Sciences of the United States of America 106, 21942-21947.
Beretta, C.A., Dross, N., Guiterrez-Triana, J.A., Ryu, S., Carl, M., 2012. Habenula circuit development: past, present, and future. Front Neurosci 6, 51.
Bianco, I.H., Wilson, S.W., 2009. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philos Trans R Soc Lond B Biol Sci 364, 1005-1020.
Blader, P., Plessy, C., Strahle, U., 2003. Multiple regulatory elements with spatially and temporally distinct activities control neurogenin1 expression in primary neurons of the zebrafish embryo. Mech Dev 120, 211-218.
Carpenter, A.C., Rao, S., Wells, J.M., Campbell, K., Lang, R.A., 2010. Generation of mice with a conditional null allele for Wntless. Genesis 48, 554-558.
Cau, E., Gradwohl, G., Casarosa, S., Kageyama, R., Guillemot, F., 2000. Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Development 127, 2323-2332.
Ching, W., Hang, H.C., Nusse, R., 2008. Lipid-independent secretion of a Drosophila Wnt protein. J Biol Chem 283, 17092-17098.
Das, S., Yu, S., Sakamori, R., Stypulkowski, E., Gao, N., 2012. Wntless in Wnt secretion: molecular, cellular and genetic aspects. Front Biol (Beijing) 7, 587-593.
deCarvalho, T.N., Akitake, C.M., Thisse, C., Thisse, B., Halpern, M.E., 2013. Aversive cues fail to activate fos expression in the asymmetric olfactory-habenula pathway of zebrafish. Front Neural Circuits 7, 98.
Gfrerer, L., Dougherty, M., Liao, E.C., 2013. Visualization of craniofacial development in the sox10: kaede transgenic zebrafish line using time-lapse confocal microscopy. J Vis Exp, e50525.
Herr, P., Basler, K., 2012. Porcupine-mediated lipidation is required for Wnt recognition by Wls. Dev Biol 361, 392-402.
Hikosaka, O., 2010. The habenula: from stress evasion to value-based decision-making. Nat Rev Neurosci 11, 503-513.
Hirabayashi, Y., Itoh, Y., Tabata, H., Nakajima, K., Akiyama, T., Masuyama, N., Gotoh, Y., 2004. The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development 131, 2791-2801.
Inestrosa, N.C., Varela-Nallar, L., 2015. Wnt signalling in neuronal differentiation and development. Cell Tissue Res 359, 215-223.
Jeong, J.Y., Einhorn, Z., Mercurio, S., Lee, S., Lau, B., Mione, M., Wilson, S.W., Guo, S., 2006. Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl. Proceedings of the National Academy of Sciences of the United States of America 103, 5143-5148.
Komiya, Y., Habas, R., 2008. Wnt signal transduction pathways. Organogenesis 4, 68-75.
Kuan, Y.S., Roberson, S., Akitake, C.M., Fortuno, L., Gamse, J., Moens, C., Halpern, M.E., 2015. Distinct requirements for Wntless in habenular development. Dev Biol 406, 117-128.
Lundell, T.G., Zhou, Q., Doughty, M.L., 2009. Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice. Dev Dyn 238, 3310-3325.
Machon, O., Backman, M., Machonova, O., Kozmik, Z., Vacik, T., Andersen, L., Krauss, S., 2007. A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus. Dev Biol 311, 223-237.
Munji, R.N., Choe, Y., Li, G., Siegenthaler, J.A., Pleasure, S.J., 2011. Wnt signaling regulates neuronal differentiation of cortical intermediate progenitors. J Neurosci 31, 1676-1687.
Pandey, S., Shekhar, K., Regev, A., Schier, A.F., 2018. Comprehensive Identification and Spatial Mapping of Habenular Neuronal Types Using Single-Cell RNA-Seq. Curr Biol 28, 1052-1065 e1057.
Pasini, A., Henrique, D., Wilkinson, D.G., 2001. The zebrafish Hairy/Enhancer-of-split-related gene her6 is segmentally expressed during the early development of hindbrain and somites. Mech Dev 100, 317-321.
Roussigne, M., Bianco, I.H., Wilson, S.W., Blader, P., 2009. Nodal signalling imposes left-right asymmetry upon neurogenesis in the habenular nuclei. Development 136, 1549-1557.
Schmidt, E.R.E., Pasterkamp, R.J., 2017. The molecular mechanisms controlling morphogenesis and wiring of the habenula. Pharmacol Biochem Behav 162, 29-37.
Scholpp, S., Delogu, A., Gilthorpe, J., Peukert, D., Schindler, S., Lumsden, A., 2009. Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus. Proceedings of the National Academy of Sciences of the United States of America 106, 19895-19900.
Shen, C., Li, L., Zhao, K., Bai, L., Wang, A., Shu, X., Xiao, Y., Zhang, J., Zhang, K., Hui, T., Chen, W., Zhang, B., Hsu, W., Xiong, W.C., Mei, L., 2018. Motoneuron Wnts regulate neuromuscular junction development. Elife 7.
Wilkinson, G., Dennis, D., Schuurmans, C., 2013. Proneural genes in neocortical development. Neuroscience 253, 256-273.
Wree, A., Zilles, K., Schleicher, A., 1981. Growth of fresh volumes and spontaneous cell death in the nuclei habenulae of albino rats during ontogenesis. Anat Embryol (Berl) 161, 419-431.
Wu, B.T., Wen, S.H., Hwang, S.P., Huang, C.J., Kuan, Y.S., 2015. Control of Wnt5b secretion by Wntless modulates chondrogenic cell proliferation through fine-tuning fgf3 expression. J Cell Sci 128, 2328-2339.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73525-
dc.description.abstract作為演化上高度保留的訊息傳遞路徑,Wnt參與了早期胚胎發育過程中的許多調控。而Wntless,對於Wnt蛋白的分泌扮演了非常重要的角色。neurogenin-1 (ngn1)是一種轉錄因子,主要表現在早期神經系統中,神經前驅細胞的區域(Progenitor zone)。作為一種神經前驅型基因(Proneural gene),ngn1參與了早期多功能幹細胞至神經細胞的分化過程。在過去的研究中發現,在Wntless突變的斑馬魚的間腦(Diencephalon),ngn1的表現量大幅度下降。而ngn1的表現量下降,很可能干擾了斑馬魚胚胎的缰核(Habenula)神經元的形成。然而,於此過程中,wls與ngn1間的調控機制目前尚不清楚。
在此,我們藉由螢光原位雜合技術 (Fluorescent in situ Hybridization)、免疫染色(Immunostaining)與3-D影像對位(3-Dimensional Image Registration)的技術,來評估在wntless突變胚胎中ngn1與her6 (一個ngn1的抑制子)之間的表現情形。並且藉由細胞譜系標記(Cell Lineage Labeling)的方式,分析ngn1啟動子驅動的細胞與韁核之間的關係。過程中發現,於間腦處的ngn1的表現量減少了近40%,而her6的表現量增加近4.5倍。而藉由分析了ngn1與her6之間的消長與空間位置的關係,顯示出在神經細胞分化的過程中,可能出現了細胞命運轉換(Cell Fate alteration)的情形。除此之外,我們的結果顯示,細胞命運轉換的現象很有可能是影響缰核發育的重要原因。
zh_TW
dc.description.abstractWnt signaling pathway is a conserved pathway regulating critical evens during embryonic development in different animals. Wls plays an important role in the secretion of Wnt protein. Neurogenin 1 (ngn1) is a transcriptional factor that is mainly expressed in the progenitor zone in the neural system. As a proneural gene, ngn1 derives the differentiation of pluripotent stem cells to neuronal subtypes. In the previous study, reduction of ngn1 expression in zebrafish wls mutant is proposed to perturb habenular neuronal development in the zebrafish embryos. However, the regulatory relationship between ngn1 and wls is still unclear.
Utilizing fluorescent in situ hybridization (FISH), immunostaining and 3-dimensional image registration techniques, the expressions of ngn1 and her6, a repressor of ngn1, in zebrafish wildtype and wls mutant embryos have been evaluated. The results indicate that ngn1 expression exhibits nearly 40% reduction whereas her6 expression exhibits 4.5 times increase in the HA progenitor zone in diencephalon of the zebrafish wls mutant embryos. The increased her6 and reduced ngn1 expressions combined with their positional relationship suggest that the alteration of cell fate occurs between the generations of diencephalic her6 and ngn1 proneurons. Our results suggest that the alteration of cell fate conceivably perturbs the development of habenular nuclei.
en
dc.description.provenanceMade available in DSpace on 2021-06-17T07:39:57Z (GMT). No. of bitstreams: 1
ntu-108-R03b46032-1.pdf: 1980823 bytes, checksum: abf2d7b2a08fe01a2fee86bc7cab280c (MD5)
Previous issue date: 2019
en
dc.description.tableofcontentsList of Abbreviations II
摘要 III
Abstract IV
Chapter I Introduction 1
1.1 Wnt signaling plays important role in neuronal development 1
1.2 Wntless is required for the release of some Wnt. 2
1.3 The ngn1 reduction in wls mutants unravels the genetic regulation in habenular development 3
1.4 Role of Hairy-related 6 (her6) in ngn1 regulation during habenular formation is still unclear. 4
1.5 Application of 3-D registration technique 5
Chapter 2 Materials and Methods 7
2.1 Zebrafish strain and husbandry 7
2.2 Whole mount RNA fluorescent in situ hybridization and immunofluorescence staining 7
2.3 3-D Reconstruction, Alignment, and Volume-rendering 7
2.4 Statistics and charts 8
2.5 Cell labeling and Lineage tracing 8
Chapter 3 Results 10
3.1 The reconstructed 3-D models confirm the previous studies suggesting the decrease of ngn1 at left and right diencephalon. 10
3.2 Up-regulation of her6 expression in diencephalon region in wls mutants. 11
3.3 Lineage alteration between ngn1 and her6 occurs in wls mutant. 11
3.4 her6 shows highly overlapped with wls-expressing cells within MDO (mid-diencephalon organizer). 12
3.5 ngn1-promoter derived cells within dorsal diencephalon construct habenular structures. 13
Chapter 4 Conclusions and Discussions 14
4.1 Function of her6 in wls-mediated ngn1 regulation within habenular region is still unclear. 14
4.2 Benefits and Difficulties in application of 3-D registration. 15
4.3 Problems in Kaede-based tracing system 16
References 18
Figures 22
dc.language.isozh-TW
dc.subject斑馬魚zh_TW
dc.subjectngn1zh_TW
dc.subjecther6zh_TW
dc.subjectwlszh_TW
dc.subject?核zh_TW
dc.subject3-D 影像對位zh_TW
dc.subject3-D registrationen
dc.subjectwlsen
dc.subjecthabenulaen
dc.subjectzebrafishen
dc.subjectngn1en
dc.subjecther6en
dc.titleWls在斑馬魚胚胎內對原神經基因表現所扮演的角色zh_TW
dc.titleRole of Wls on Proneural Gene Expression in Zebrafish Embryosen
dc.typeThesis
dc.date.schoolyear107-1
dc.description.degree碩士
dc.contributor.oralexamcommittee胡清華,江運金,黃聲蘋
dc.subject.keywordngn1,her6,wls,?核,斑馬魚,3-D 影像對位,zh_TW
dc.subject.keywordngn1,her6,wls,habenula,zebrafish,3-D registration,en
dc.relation.page47
dc.identifier.doi10.6342/NTU201900605
dc.rights.note有償授權
dc.date.accepted2019-02-15
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept生化科學研究所zh_TW
顯示於系所單位:生化科學研究所

文件中的檔案:
檔案 大小格式 
ntu-108-1.pdf
  未授權公開取用
1.93 MBAdobe PDF
顯示文件簡單紀錄


系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved