請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8939完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Tsai-Fang Huang | en |
| dc.contributor.author | 黃才芳 | zh_TW |
| dc.date.accessioned | 2021-05-20T20:04:37Z | - |
| dc.date.available | 2010-08-20 | |
| dc.date.available | 2021-05-20T20:04:37Z | - |
| dc.date.copyright | 2009-08-20 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-08-17 | |
| dc.identifier.citation | Reference
Agawa, Y., Sarhan, M., Kageyama, Y., Akagi, K., Takai, M., Hashiyama, K., Wada, T., Handa, H., Iwamatsu, A., Hirose, S. et al. 2007. Drosophila Blimp-1 is a transient transcriptional repressor that controls timing of the ecdysone-induced developmental pathway. Mol Cell Biol 27(24): 8739-8747. Altun-Gultekin, Z., Andachi, Y., Tsalik, E.L., Pilgrim, D., Kohara, Y., and Hobert, O. 2001. A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. Development 128(11): 1951-1969. Ambros, V. 2000. Control of developmental timing in Caenorhabditis elegans. Curr Opin Genet Dev 10(4): 428-433. Andersen, E.C. and Horvitz, H.R. 2007. Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development. Development 134(16): 2991-2999. Antebi, A., Norris, C.R., Hedgecock, E.M. and Garriga, G. 1997. Cell and growth cone migrations. Celegans II (ed DL Riddle, T Blumenthal, BJ Meyer and JR Priess): pp.583-609. Antebi, A., Yeh, W.H., Tait, D., Hedgecock, E.M., and Riddle, D.L. 2000. daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes Dev 14(12): 1512-1527. Battye, R., Stevens, A., and Jacobs, J.R. 1999. Axon repulsion from the midline of the Drosophila CNS requires slit function. Development 126(11): 2475-2481. Baxendale, S., Davison, C., Muxworthy, C., Wolff, C., Ingham, P.W., and Roy, S. 2004. The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling. Nat Genet 36(1): 88-93. Bethke, A., Fielenbach, N., Wang, Z., Mangelsdorf, D.J., and Antebi, A. 2009. Nuclear hormone receptor regulation of microRNAs controls developmental progression. Science 324(5923): 95-98. Bettinger, J.C., Lee, K., and Rougvie, A.E. 1996. Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. Development 122(8): 2517-2527. Blelloch, R., Anna-Arriola, S.S., Gao, D., Li, Y., Hodgkin, J., and Kimble, J. 1999. The gon-1 gene is required for gonadal morphogenesis in Caenorhabditis elegans. Dev Biol 216(1): 382-393. Blelloch, R. and Kimble, J. 1999. Control of organ shape by a secreted metalloprotease in the nematode Caenorhabditis elegans. Nature 399(6736): 586-590. Brenner, S. 1974. The genetics of Caenorhabditis elegans. Genetics 77(1): 71-94. Calame, K. 2008. Activation-dependent induction of Blimp-1. Curr Opin Immunol 20(3): 259-264. Chan, S.S., Zheng, H., Su, M.W., Wilk, R., Killeen, M.T., Hedgecock, E.M., and Culotti, J.G. 1996. UNC-40, a C. elegans homolog of DCC (Deleted in Colorectal Cancer), is required in motile cells responding to UNC-6 netrin cues. Cell 87(2): 187-195. Chilton, J.K. 2006. Molecular mechanisms of axon guidance. Dev Biol 292(1): 13-24. Colavita, A. and Culotti, J.G. 1998. Suppressors of ectopic UNC-5 growth cone steering identify eight genes involved in axon guidance in Caenorhabditis elegans. Dev Biol 194(1): 72-85. Colavita, A., Krishna, S., Zheng, H., Padgett, R.W., and Culotti, J.G. 1998. Pioneer axon guidance by UNC-129, a C. elegans TGF-beta. Science 281(5377): 706-709. Crowner, D., Madden, K., Goeke, S., and Giniger, E. 2002. Lola regulates midline crossing of CNS axons in Drosophila. Development 129(6): 1317-1325. Culotti, J.G. and Merz, D.C. 1998. DCC and netrins. Curr Opin Cell Biol 10(5): 609-613. Doody, G.M., Stephenson, S., McManamy, C., and Tooze, R.M. 2007. PRDM1/BLIMP-1 modulates IFN-gamma-dependent control of the MHC class I antigen-processing and peptide-loading pathway. J Immunol 179(11): 7614-7623. Drescher, U., Kremoser, C., Handwerker, C., Loschinger, J., Noda, M., and Bonhoeffer, F. 1995. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82(3): 359-370. Dufourcq, P., Victor, M., Gay, F., Calvo, D., Hodgkin, J., and Shi, Y. 2002. Functional requirement for histone deacetylase 1 in Caenorhabditis elegans gonadogenesis. Mol Cell Biol 22(9): 3024-3034. Eickholt, B.J. 2008. Functional diversity and mechanisms of action of the semaphorins. Development 135(16): 2689-2694. Fielenbach, N. and Antebi, A. 2008. C. elegans dauer formation and the molecular basis of plasticity. Genes Dev 22(16): 2149-2165. Fielenbach, N., Guardavaccaro, D., Neubert, K., Chan, T., Li, D., Feng, Q., Hutter, H., Pagano, M., and Antebi, A. 2007. DRE-1: an evolutionarily conserved F box protein that regulates C. elegans developmental age. Dev Cell 12(3): 443-455. Finney, M. and Ruvkun, G. 1990. The unc-86 gene product couples cell lineage and cell identity in C. elegans. Cell 63(5): 895-905. Fradkin, L.G., Noordermeer, J.N., and Nusse, R. 1995. The Drosophila Wnt protein DWnt-3 is a secreted glycoprotein localized on the axon tracts of the embryonic CNS. Dev Biol 168(1): 202-213. Ghosh, N., Gyory, I., Wright, G., Wood, J., and Wright, K.L. 2001. Positive regulatory domain I binding factor 1 silences class II transactivator expression in multiple myeloma cells. J Biol Chem 276(18): 15264-15268. Gyory, I., Wu, J., Fejer, G., Seto, E., and Wright, K.L. 2004. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nat Immunol 5(3): 299-308. Epub 2004 Feb 2022. Hedgecock, E.M., Culotti, J.G., and Hall, D.H. 1990a. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4(1): 61-85. Hedgecock, E.M., Culotti, J.G., and Hall, D.H. 1990b. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4(1): 61-85. Hedgecock, E.M., Culotti, J.G., Hall, D.H., and Stern, B.D. 1987. Genetics of cell and axon migrations in Caenorhabditis elegans. Development 100(3): 365-382. Hirai, H., Maru, Y., Hagiwara, K., Nishida, J., and Takaku, F. 1987. A novel putative tyrosine kinase receptor encoded by the eph gene. Science 238(4834): 1717-1720. Huang, S., Shao, G., and Liu, L. 1998. The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J Biol Chem 273(26): 15933-15939. Ishii, N., Wadsworth, W.G., Stern, B.D., Culotti, J.G., and Hedgecock, E.M. 1992. UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans. Neuron 9(5): 873-881. Jeon, M., Gardner, H.F., Miller, E.A., Deshler, J., and Rougvie, A.E. 1999. Similarity of the C. elegans developmental timing protein LIN-42 to circadian rhythm proteins. Science 286(5442): 1141-1146. Kamath, R.S., Martinez-Campos, M., Zipperlen, P., Fraser, A.G., and Ahringer, J. 2001. Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biol 2(1): RESEARCH0002. Keller, A.D. and Maniatis, T. 1991. Identification and characterization of a novel repressor of beta-interferon gene expression. Genes Dev 5(5): 868-879. Kidd, T., Bland, K.S., and Goodman, C.S. 1999. Slit is the midline repellent for the robo receptor in Drosophila. Cell 96(6): 785-794. Killeen, M.T. and Sybingco, S.S. 2008. Netrin, Slit and Wnt receptors allow axons to choose the axis of migration. Dev Biol 323(2): 143-151. Kimble, J. and Hirsh, D. 1979. The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev Biol 70(2): 396-417. Kouzarides, T. 2002. Histone methylation in transcriptional control. Curr Opin Genet Dev 12(2): 198-209. Kuo, T.C. and Calame, K.L. 2004. B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites. J Immunol 173(9): 5556-5563. Labrador, J.P., O'Keefe, D., Yoshikawa, S., McKinnon, R.D., Thomas, J.B., and Bashaw, G.J. 2005. The homeobox transcription factor even-skipped regulates netrin-receptor expression to control dorsal motor-axon projections in Drosophila. Curr Biol 15(15): 1413-1419. Larrivee, B., Freitas, C., Trombe, M., Lv, X., Delafarge, B., Yuan, L., Bouvree, K., Breant, C., Del Toro, R., Brechot, N. et al. 2007. Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis. Genes Dev 21(19): 2433-2447. Lehmann, R. 2001. Cell migration in invertebrates: clues from border and distal tip cells. Curr Opin Genet Dev 11(4): 457-463. Leung-Hagesteijn, C., Spence, A.M., Stern, B.D., Zhou, Y., Su, M.W., Hedgecock, E.M., and Culotti, J.G. 1992. UNC-5, a transmembrane protein with immunoglobulin and thrombospondin type 1 domains, guides cell and pioneer axon migrations in C. elegans. Cell 71(2): 289-299. Levy-Strumpf, N. and Culotti, J.G. 2007. VAB-8, UNC-73 and MIG-2 regulate axon polarity and cell migration functions of UNC-40 in C. elegans. Nat Neurosci 10(2): 161-168. Lin, Y., Wong, K., and Calame, K. 1997. Repression of c-myc transcription by Blimp-1, an inducer of terminal B cell differentiation. Science 276(5312): 596-599. Ludewig, A.H., Kober-Eisermann, C., Weitzel, C., Bethke, A., Neubert, K., Gerisch, B., Hutter, H., and Antebi, A. 2004. A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging. Genes Dev 18(17): 2120-2133. Ly, N.P., Komatsuzaki, K., Fraser, I.P., Tseng, A.A., Prodhan, P., Moore, K.J., and Kinane, T.B. 2005. Netrin-1 inhibits leukocyte migration in vitro and in vivo. Proc Natl Acad Sci U S A 102(41): 14729-14734. MacNeil, L.T., Hardy, W.R., Pawson, T., Wrana, J.L., and Culotti, J.G. 2009. UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways. Nat Neurosci 12(2): 150-155. Magnusdottir, E., Kalachikov, S., Mizukoshi, K., Savitsky, D., Ishida-Yamamoto, A., Panteleyev, A.A., and Calame, K. 2007. Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1. Proc Natl Acad Sci U S A 104(38): 14988-14993. Maloof, J.N., Whangbo, J., Harris, J.M., Jongeward, G.D., and Kenyon, C. 1999. A Wnt signaling pathway controls hox gene expression and neuroblast migration in C. elegans. Development 126(1): 37-49. Martins, G. and Calame, K. 2008. Regulation and functions of Blimp-1 in T and B lymphocytes. Annu Rev Immunol 26: 133-169. Miller, D.M., 3rd, Niemeyer, C.J., and Chitkara, P. 1993. Dominant unc-37 mutations suppress the movement defect of a homeodomain mutation in unc-4, a neural specificity gene in Caenorhabditis elegans. Genetics 135(3): 741-753. Montell, D.J. 1999. The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development. Development 126(14): 3035-3046. Nash, B., Colavita, A., Zheng, H., Roy, P.J., and Culotti, J.G. 2000. The forkhead transcription factor UNC-130 is required for the graded spatial expression of the UNC-129 TGF-beta guidance factor in C. elegans. Genes Dev 14(19): 2486-2500. Nishiwaki, K., Kubota, Y., Chigira, Y., Roy, S.K., Suzuki, M., Schvarzstein, M., Jigami, Y., Hisamoto, N., and Matsumoto, K. 2004. An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans. Nat Cell Biol 6(1): 31-37. Okada, A., Charron, F., Morin, S., Shin, D.S., Wong, K., Fabre, P.J., Tessier-Lavigne, M., and McConnell, S.K. 2006. Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature 444(7117): 369-373. Perrone, C.A., Yang, P., O'Toole, E., Sale, W.S., and Porter, M.E. 1998. The Chlamydomonas IDA7 locus encodes a 140-kDa dynein intermediate chain required to assemble the I1 inner arm complex. Mol Biol Cell 9(12): 3351-3365. Pflugrad, A., Meir, J.Y., Barnes, T.M., and Miller, D.M., 3rd. 1997. The Groucho-like transcription factor UNC-37 functions with the neural specificity gene unc-4 to govern motor neuron identity in C. elegans. Development 124(9): 1699-1709. Piskurich, J.F., Lin, K.I., Lin, Y., Wang, Y., Ting, J.P., and Calame, K. 2000. BLIMP-I mediates extinction of major histocompatibility class II transactivator expression in plasma cells. Nat Immunol 1(6): 526-532. Ren, B., Chee, K.J., Kim, T.H., and Maniatis, T. 1999. PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins. Genes Dev 13(1): 125-137. Rothberg, J.M., Jacobs, J.R., Goodman, C.S., and Artavanis-Tsakonas, S. 1990. slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. Genes Dev 4(12A): 2169-2187. Rowse-Eagle, D., Watson, H.D., and Tignor, G.H. 1981. Improved method for trypsin digestion of Paraplast sections before immunofluorescence staining. J Clin Microbiol 13(5): 996-997. Seeger, M., Tear, G., Ferres-Marco, D., and Goodman, C.S. 1993. Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron 10(3): 409-426. Shostak, Y., Van Gilst, M.R., Antebi, A., and Yamamoto, K.R. 2004. Identification of C. elegans DAF-12-binding sites, response elements, and target genes. Genes Dev 18(20): 2529-2544. Su, M., Merz, D.C., Killeen, M.T., Zhou, Y., Zheng, H., Kramer, J.M., Hedgecock, E.M., and Culotti, J.G. 2000a. Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal tip cells in Caenorhabditis elegans. Development 127(3): 585-594. Su, M., Merz, D.C., Killeen, M.T., Zhou, Y., Zheng, H., Kramer, J.M., Hedgecock, E.M., and Culotti, J.G. 2000b. Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal tip cells in Caenorhabditis elegans. Development 127(3): 585-594. Sulston, J.E. and Horvitz, H.R. 1977. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56(1): 110-156. Sulston, J.E.a.H., J. 1988. The Nematode Caenorhabditis elegans Methods. Cold Spring Habor Laboratory Press. Tamai, K.K. and Nishiwaki, K. 2007. bHLH transcription factors regulate organ morphogenesis via activation of an ADAMTS protease in C. elegans. Dev Biol 308(2): 562-571. Tennessen, J.M., Gardner, H.F., Volk, M.L., and Rougvie, A.E. 2006. Novel heterochronic functions of the Caenorhabditis elegans period-related protein LIN-42. Dev Biol 289(1): 30-43. Tooze, R.M., Stephenson, S., and Doody, G.M. 2006. Repression of IFN-gamma induction of class II transactivator: a role for PRDM1/Blimp-1 in regulation of cytokine signaling. J Immunol 177(7): 4584-4593. Turner, C.A., Jr., Mack, D.H., and Davis, M.M. 1994. Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells. Cell 77(2): 297-306. Wadsworth, W.G., Bhatt, H., and Hedgecock, E.M. 1996. Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron 16(1): 35-46. Whangbo, J. and Kenyon, C. 1999. A Wnt signaling system that specifies two patterns of cell migration in C. elegans. Mol Cell 4(5): 851-858. Wicks, S.R., Yeh, R.T., Gish, W.R., Waterston, R.H., and Plasterk, R.H. 2001. Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nat Genet 28(2): 160-164. Williams, B.D., Schrank, B., Huynh, C., Shownkeen, R., and Waterston, R.H. 1992. A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites. Genetics 131(3): 609-624. Wu, Y.C., Cheng, T.W., Lee, M.C., and Weng, N.Y. 2002. Distinct rac activation pathways control Caenorhabditis elegans cell migration and axon outgrowth. Dev Biol 250(1): 145-155. Yu, J., Angelin-Duclos, C., Greenwood, J., Liao, J., and Calame, K. 2000. Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Mol Cell Biol 20(7): 2592-2603. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8939 | - |
| dc.description.abstract | 細胞遷移在生物發育過程中扮演著重要的角色，細胞在什麼時間遷移到哪個地點，都必須經過嚴格的控制；現階段對細胞遷移的研究，僅針對時間或空間調控的個別探討，而整合兩者調控的相關機制目前瞭解得很少。在雌雄同體的線蟲個體中，有兩顆DTC細胞在特定的發育時期會進行特定的遷移路徑，這樣的遷移路徑也決定日後生殖腺的形狀。在DTC爬行過程中，荷爾蒙接收器DAF-12、F box蛋白質DRE-1及轉錄調控子LIN-29負責共同調控DTC在三齡幼蟲時期的遷移，其中包含了DTC從腹側到背側的背向遷移；此背向遷移需要DTC細胞表現UNC-5接收器，只要DTC表現UNC-5接收器，DTC便會接收到位在腹側Netrin蛋白質的排斥訊息，而遷移到線蟲的背側。在本研究中，我們分析dpy-24突變株、研究dpy-24基因，發現dpy-24能藉由整合三齡幼蟲發育時期的時間訊息及UNC-5腹側排斥的空間訊息，來調控DTC的背向遷移；當dpy-24發生突變時，DTC背向遷移會提早發生，而當dpy-24過度表現時，DTC的背向遷移則會延遲發生。DPY-24是一個具有zinc fingers的蛋白質，和哺乳類的轉錄抑制子Blimp-1和PRDI-BF1非常相似。藉由對unc-5轉錄表現的觀察，我們發現dpy-24會抑制unc-5的轉錄來阻止DTC提早進行背向遷移，之後免疫染色的結果顯現DPY-24在DTC中僅表現在DTC進行背向遷移之前，當DTC開始進行背向遷移後，DPY-24的表現便消失了。我們發現dre-1、daf-12與lin-29共同負責DPY-24在三齡幼蟲時期的削減，DPY-24在二齡幼蟲時期表現量最高，因此才能阻止DTC在不正確時間的背向遷移；而三齡幼蟲時期的時間訊息讓DPY-24消失，於是DPY-24不再抑制unc-5的轉錄，再加上此時LIN-29和DAF-12對於unc-5的活化，使得unc-5得以開始表現，在UNC-5順利表現後，DTC才能進行背向遷移。這個研究成果提供了一個在發育過程中，藉由整合時間與空間的訊息來調控特定細胞遷移的分子機制。 | zh_TW |
| dc.description.abstract | Cell migration plays a key role in animal development and must be temporally and spatially regulated. However, little is known about how temporal and directional signals are integrated to give rise to specific cell migration patterns. In the C. elegans hermaphrodite, two somatic distal tip cells (DTC) undergo a developmental stage- and direction-specific migration pattern which determines the shape of the gonad. The heterochronic genes daf-12, dre-1 and lin-29, encoding steroid hormone receptor, F-box protein, and zinc finger transcription factor, respectively, act together to control the third larval (L3) developmental program of the gonad, including the ventral-to-dorsal migration of the DTCs. The guidance receptor unc-5 is both necessary and sufficient for dorsal migration of the DTCs away from the ventrally concentrated extracellular cue netrin. Here, we identify and characterize dpy-24 mutants and show that dpy-24 links the L3 temporal signal to the spatial regulator unc-5 and thereby controls the timing of DTC dorsal migration. Mutations in dpy-24 results in precocious dorsalward turning of the DTCs, whereas constitutive expression of dpy-24 leads to retarded DTC dorsal turn. dpy-24 encodes a zinc-finger-containing protein, similar to mammalian transcription repressors Blimp-1 and PRDI-BF1. Using an unc-5 transcriptional gfp reporter, we show that dpy-24 prevents the DTCs from precocious dorsal turn by transcriptional repression of unc-5. The immunostaining data reveals that DPY-24 is present in the DTCs prior to their dorsalward turning and disappears during and after the dorsal turn. Further studies indicate that dre-1, daf-12 and lin-29 are responsible for DPY-24 down-regulation at the L3 stage. DPY-24 protein level is high in L2 and thus prevents DTC from dorsalward turning. The timely disappearance of DPY-24, which is regulated by L3-specific temporal signal, leads to concomitant unc-5 transcriptional up-regulation, likely mediated through transcription activities of LIN-29 and DAF-12, hence allowing DTC migration to switch towards the dorsal direction. These results provide a molecular mechanism by which temporal and spatial signals are integrated to control the precise cell migration pattern during development. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T20:04:37Z (GMT). No. of bitstreams: 1 ntu-98-F88225009-1.pdf: 3649016 bytes, checksum: 4b44f0ebd75431366142bb071903520b (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | Table of Contents
致謝 i 中文摘要 ii Abstract iv Introduction 1 Cell migration is important in development 1 DTCs provide a paradigm to study the spatiotemporal control of cell migration in C.elegans 2 Genes affecting DTC motility and polarity 3 The guidance control of DTC migration 4 The temporal control of DTC migration 6 Material and Methods 8 Strains and Genetics 8 EMS mutagenesiss 8 dpy-24 cloning and cDNA construction 9 Transgenic strains 9 Antibodies and Immunostaining 10 RNA interference 11 Yeast assay 11 Results 13 dpy-24 mutants are defective in DTC migration 13 dpy-24 mutants have a precocious DTC dorsal turn at the early L3 stage 14 DPY-24 encodes a protein with a PR domain and five zinc fingers related to the mammalian protein Blimp-1 and PRDI/BF1 15 DPY-24 is transiently present in DTCs before dorsal turn but absent after dorsal turn. 17 Constitutive expression of dpy-24 delays dorsal phase II migration 17 The precocious dorsal turn of dpy-24 mutants requires canonical Netrin/Unc-5 pathway. 18 dpy-24 represses unc-5 transcription to prevent precocious dorsal turn of DTCs. 19 The zinc fingers of DPY-24 bind directly to the unc-5 promoter at D1 and D2 sties. 21 It is difficult to reveal the biological significance of D1 and D2. 22 Down-regulation of DPY-24 is controlled by the heterochronic genes dre-1, daf-12 and lin-29 24 DAF-12 activates unc-5 transcription 25 LIN-29 activates unc-5 transcription 26 DPY-24 transcriptionally represses lin-29 in phase I DTC migration 27 Discussion 29 A functional link between a transcription factor and a guidance receptor 29 dpy-24 is a heterochronic gene 29 Transcriptional control of unc-5 31 dpy-24 likely acts in parallel to unc-5 to control the direction of the centripetal phase III migration of DTCs 32 Multiple regions of DPY-24 are important for DTC migration 33 DPY-24 down-regulation is controlled by heterochronic genes daf-12, dre-1 and lin-29 to initiate the dorsalward turning of DTCs 34 lin-42 might play as a switch for DTCs making dorsal turns or not 35 UNC5B might be the target of Blimp-1 during lymphocyte chemostasis 36 Evolutionary conservation of DPY-24 and Blimp-1 genes in the control of cell identities during development 36 Reference 38 Figures and Tables 48 Figure 1. DTC migration defects in dpy-24 mutants. 48 Figure 2. dpy-24 mutant exhibits white patches under dissecting microscope. 49 Figure 3. The migration speed of DTC in dpy-24 mutant is similar to that in N2 wild type. 50 Figure 4. DTC makes a precocious dorsal turn in dpy-24 mutant. 52 Figure 5. DTC makes its dorsal turn 3.5 hr earlier in dpy-24 mutant than in N2 wild type. 53 Figure 6. The genetic mapping and molecular cloning of dpy-24. 54 Figure 7. The dpy-24 gene and protein. 55 Figure 8. Dpy-24 expression pattern. 56 Figure 9. DPY-24 expression is transient in the first phase of DTC migration and its expression is complementary to unc-5 expression. 57 Figure 10. unc-5 is precociously activated in dpy-24 mutant and is suppressed when dpy-24 is ectopically expressed. 58 Figure 11. DPY-24 binds to t the unc-5 promoter via its zinc fingers. 60 Figure 12. DPY-24 is abnormally present in the DTCs of lin-29;daf-12, lin-29;dre-1 and dre-1;daf-12 double mutants at the L4 stage. 61 Fig 13. DAF-12 directly binds to the unc-5 promoter. 62 Figure 14. DAF-12 itself could activate the unc-5 promoter. 63 Figure 15. unc-5 expression is absent in lin-29;daf-12 double mutant. 64 Fig 16. dpy-24 suppresses the transcription of lin-29 in early L2. 65 Fig 17. The model of the interaction between dpy-24 and heterochronic genes to regulate the expression of unc-5. 66 Table 1. DTC migration patterns in dpy-24 mutants and transgenic worms 67 Table 2. Genetic interactions of dpy-24 with unc-5, unc-6, unc-40 and unc-129. 68 Table 3. The genetic interaction between dpy-24 and heterochronic genes lin-29, dre-1 and daf-12 in posterior DTC migration. 69 Table 4. Ectopic expression of lin-29 is sufficient to induce DTC dorsal turn and unc-5 expression. 70 | |
| dc.language.iso | en | |
| dc.title | 線蟲dpy-24基因整合在DTC細胞遷移過程中時間與空間的訊息調控 | zh_TW |
| dc.title | Caenorhabditis elegans dpy-24 integrates the temporal and spatial signals to control DTC migration | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 周子賓(Tze-Bin Chou),廖秀娟(Vivian H.-C. Liao),陳瑞華(Ruey-Hwa Chen),簡正鼎(Cheng-Ting Chien) | |
| dc.subject.keyword | 線蟲,細胞遷移,時間調控,異時基因,dpy-24, | zh_TW |
| dc.subject.keyword | cell migration,temporal regulation,distal tip cell (DTC),heterochronic,dpy-24,unc-5, | en |
| dc.relation.page | 70 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2009-08-17 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-98-1.pdf | 3.56 MB | Adobe PDF | 檢視/開啟 |
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。