Echinoid (Ed) 位在Adherens Junctions（AJs），是一個包括免疫球蛋白區域的同型性細胞黏著分子並與DE-Cadherin合作負責細胞間的黏合。Ed參與胚胎背部表皮細胞閉鎖的過程，此形態發生事件為協同細胞形態的改變以及細胞移動覆蓋amnioserosa (AS) 然後移動到正確的位置上縫合。除了AS外，Ed分布在整個表皮細胞上。Ed協調細胞的移動、參與細胞形態的改變、actomyosin cable及filopodial protrusion的形成，但並不會影響JNK訊號傳遞。而Ed參與細胞形態的改變是需要intracellular domain (Edintra)的存在。Ed在in vivo中可形成同型二聚體，而Edintra單體可直接和unconventional myosin VI/Jaguar (Jar) 結合。genetic interaction 實驗中證明ed 和jar一起調控細胞形態的改變。之前的文獻指出在in vitro中myosin VI以單體型式存在，而形成同型二聚體可以結合沿著actin filaments 移動。因此，我們認為in vivo中Ed可促使myosin VI形成二聚體，進而調控actin filaments而造成細胞形態的改變。另外我們也發現在AS額外表現ed會造成細胞收縮，而此結果是透過myosin VI所造成的。

Echinoid (Ed) is a homophilic immunoglobulin domain-containing molecule (CAM) that localizes to adherens junctions (AJs) and cooperates with Drosophila melanogaster epithelial (DE)-cadherin to mediate cell adhesion. Here we show that Ed takes part in many processes of dorsal closure, a morphogenetic movement driven by coordinated cell shape changes and migration of epidermal cells to cover the underlying amnioserosa. Ed is differentially expressed, appearing in epidermis but not in amnioserosa cells. Ed functions independently from the JNK signaling pathway and is required to regulate cell morphology, and for assembly of actomyosin cable, filopodial protrusion and coordinated cell migration in dorsal-most epidermal cells. The effect of Ed on cell morphology requires the presence of the intracellular domain (Edintra). Interestingly, Ed forms homodimers in vivo and Edintra monomer directly associates with unconventional (Jar) motor protein. We further show that ed genetically interacts with jar to control cell morphology. It has previously been shown that myosin VI is monomeric in vitro and that its dimeric form can associate with and travel processively along actin filaments. Thus, we propose that Ed mediates the dimerization of myosin VI/Jar in vivo which in turn regulates the reorganization and/or contraction of actin filaments to control changes in cell shape. Consistent with this, we found that ectopic ed expression in the amnioserosa induces myosin VI/Jar-dependent apical constriction of this tissue.

Ahmed, A., Chandra, S., Magarinos, M., Vaessin, H., 2003. Echinoid mutants exhibit neurogenic phenotypes and show synergistic interactions with the Notch signaling pathway. Development 130, 6295-6304.
Altman, D., Sweeney, H. L., Spudich, J. A., 2004. The mechanism of myosin VI translocation and its load-induced anchoring. Cell 116, 737-749.
Amano, M., Ito, M., Kimura, K., Fukata, Y., Chihara, K., Nakano, T., Matsuura, Y., Kaibuchi, K., 1996. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol. Chem. 271, 20246-20249.
Bai, J. M., Chiu, W. H., Wang, J. C., Tzeng, T. H., Perrimon, N., Hsu, J. C., 2001. The cell adhesion molecule Echinoid defines a new pathway that antagonizes the Drosophila EGF receptor signaling pathway. Development 128, 591-601.
Bishop, A. L., Hall, A., 2000. Rho GTPases and their effector proteins. Biochem J. 348 Pt 2, 241-255.
Bloor, J. W., Kiehart, D. P., 2002. Drosophila RhoA regulates the cytoskeleton and cell-cell adhesion in the developing epidermis. Development 129, 3173-3183.
Brand, A. H., Perrimon, N., 1993. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401-415.
Bresnick, A. R., 1999. Molecular mechanisms of nonmuscle myosin-II regulation. Curr. Opin. Cell Biol. 11, 26-33.
Buss, F., Luzio, J. P., Kendrick-Jones, J., 2002. Myosin VI, an actin motor for membrane traffic and cell migration. Traffic 3, 851-858.
Chen, L. Y., Wang, J. C., Hyvert, Y., Lin, H. P., Perrimon, N., Imler, J. L., Hsu, J. C., 2006. Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo. Curr. Biol. 16, 1183-1193.
Chen, X., Gumbiner, B. M., 2006. Crosstalk between different adhesion molecules. Curr. Opin. Cell Biol. 18, 572-578.
Chou, T. B., Perrimon, N., 1996. The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics 144, 1673-1679.
Cramer, L. P., 2000. Myosin VI: roles for a minus end-directed actin motor in cells. J. Cell Biol. 150, F121-126.
Escudero, L. M., Wei, S. Y., Chiu, W. H., Modolell, J., Hsu, J. C., 2003. Echinoid synergizes with the Notch signaling pathway in Drosophila mesothorax bristle patterning. Development 130, 6305-6316.
Franke, J. D., Montague, R. A., Kiehart, D. P., 2005. Nonmuscle myosin II generates forces that transmit tension and drive contraction in multiple tissues during dorsal closure. Curr. Biol. 15, 2208-2221.
Fox, D. T., Peifer, M., 2007. Abelson kinase (Abl) and RhoGEF2 regulate actin organization during cell constriction in Drosophila. Development 134, 567-578.
Gates, J., Mahaffey, J. P., Rogers, S. L., Emerson, M., Rogers, E. M., Sottile, S. L., Van Vactor, D., Gertler, F. B., Peifer, M., 2007. Enabled plays key roles in embryonic epithelial morphogenesis in Drosophila. Development 134, 2027-2039.
Geisbrecht, E. R., Montell, D. J., 2002. Myosin VI is required for E-cadherin-mediated border cell migration. Nat. Cell Biol. 4, 616-620.
Genova, J. L., Jong, S., Camp, J. T., Fehon, R. G. 2000. Functional analysis of Cdc42 in actin filament assembly, epithelial morphogenesis, and cell signaling during Drosophila development. Dev. Biol. 221, 181-94.
Glise, B., Noselli, S., 1997. Coupling of Jun amino-terminal kinase and Decapentaplegic signaling pathways in Drosophila morphogenesis. Genes Dev. 11, 1738-1747.
Grevengoed, E. E., Loureiro, J. J., Jesse, T. L., Peifer, M., 2001. Abelson kinase regulates epithelial morphogenesis in Drosophila. J. Cell Biol. 155, 1185-1198.
Halsell, S. R., Chu, B. I., Kiehart, D. P., 2000. Genetic analysis demonstrates a direct link between rho signaling and nonmuscle myosin function during Drosophila morphogenesis. Genetics 155, 1253-1265.
Harden, N., 2002. Signaling pathways directing the movement and fusion of epithelial sheets: lessons from dorsal closure in Drosophila. Differentiation 70, 181-203.
Harden, N., Ricos, M., Ong, Y. M., Chia, W., Lim, L., 1999. Participation of small GTPases in dorsal closure of the Drosophila embryo: distinct roles for Rho subfamily proteins in epithelial morphogenesis. J. Cell Sci. 112 , 273-284.
Harden, N., Ricos, M., Yee, K., Sanny, J., Langmann, C., Yu, H., Chia, W., Lim, L., 2002. Drac1 and Crumbs participate in amnioserosa morphogenesis during dorsal closure in Drosophila. J. Cell Sci. 115, 2119-2129.
Holmes, K. C., Geeves, M. A., 2000. The structural basis of muscle contraction. Philos Trans R Soc Lond B Biol Sci 355, 419-431.
Hutson, M. S., Tokutake, Y., Chang, M. S., Bloor, J. W., Venakides, S., Kiehart, D. P., Edwards, G. S., 2003. Forces for morphogenesis investigated with laser microsurgery and quantitative modeling. Science 300, 145-149.
Islam, R., Wei, S. Y., Chiu, W. H., Hortsch, M., Hsu, J. C., 2003. Neuroglian activates Echinoid to antagonize the Drosophila EGF receptor signaling pathway. Development 130, 2051-2059.
Jacinto, A., Martinez-Arias, A., Martin, P., 2001. Mechanisms of epithelial fusion and repair. Nat Cell Biol. 3, E117-123.
Jacinto, A., Wood, W., Balayo, T., Turmaine, M., Martinez-Arias, A., Martin, P., 2000. Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure. Curr. Biol. 10, 1420-1426.
Jacinto, A., Wood, W., Woolner, S., Hiley, C., Turner, L., Wilson, C., Martinez-Arias, A., Martin, P., 2002a. Dynamic analysis of actin cable function during Drosophila dorsal closure. Curr. Biol. 12, 1245-1250.
Jacinto, A., Woolner, S., Martin, P., 2002b. Dynamic analysis of dorsal closure in Drosophila: from genetics to cell biology. Dev. Cell 3, 9-19.
Kaltschmidt, J. A., Lawrence, N., Morel, V., Balayo, T., Fernandez, B. G., Pelissier, A., Jacinto, A., Martinez Arias, A., 2002. Planar polarity and actin dynamics in the epidermis of Drosophila. Nat. Cell Biol. 4, 937-944.
Karess, R. E., Chang, X. J., Edwards, K. A., Kulkarni, S., Aguilera, I., Kiehart, D. P., 1991. The regulatory light chain of nonmuscle myosin is encoded by spaghetti-squash, a gene required for cytokinesis in Drosophila. Cell 65, 1177-1189.
Kiehart, D. P., Galbraith, C. G., Edwards, K. A., Rickoll, W. L., Montague, R. A., 2000. Multiple forces contribute to cell sheet morphogenesis for dorsal closure in Drosophila. J. Cell Biol. 149, 471-490.
Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A., Kaibuchi, K., 1996. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273, 245-248.
Laplante, C., Nilson, L. A., 2006. Differential expression of the adhesion molecule Echinoid drives epithelial morphogenesis in Drosophila. Development 133, 3255-3264.
Lawrence, N., Morel, V., 2003. Dorsal closure and convergent extension: two polarised morphogenetic movements controlled by similar mechanisms? Mech Dev 120, 1385-1393.
Lister, I., Roberts, R., Schmitz, S., Walker, M., Trinick, J., Veigel, C., Buss, F., Kendrick-Jones, J., 2004. Myosin VI: a multifunctional motor. Biochem. Soc. Trans. 32, 685-688.
Lu, Y., Settleman, J., 1999. The Drosophila Pkn protein kinase is a Rho/Rac effector target required for dorsal closure during embryogenesis. Genes Dev. 13, 1168-1180.
Magie, C. R., Meyer, M. R., Gorsuch, M. S., Parkhurst, S. M., 1999. Mutations in the Rho1 small GTPase disrupt morphogenesis and segmentation during early Drosophila development. Development 126, 5353-5364.
Magie, C. R., Pinto-Santini, D., Parkhurst, S. M., 2002. Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila. Development 129, 3771-3782.
Martin-Blanco, E., Gampel, A., Ring, J., Virdee, K., Kirov, N., Tolkovsky, A. M., Martinez-Arias, A., 1998. Puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev. 12, 557-570.
Martin, P., Parkhurst, S. M., 2004. Parallels between tissue repair and embryo morphogenesis. Development 131, 3021-3034.
Millo, H., Leaper, K., Lazou, V., Bownes, M., 2004. Myosin VI plays a role in cell-cell adhesion during epithelial morphogenesis. Mech. Dev. 121, 1335-1351.
Mizuno, T., Tsutsui, K., Nishida, Y., 2002. Drosophila myosin phosphatase and its role in dorsal closure. Development 129, 1215-1223.
Muller, H. A., Wieschaus, E., 1996. Armadillo, Bazooka, and Stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila. J. Cell Biol. 134, 149-163.
Nishikawa, S., Homma, K., Komori, Y., Iwaki, M., Wazawa, T., Hikikoshi Iwane, A., Saito, J., Ikebe, R., Katayama, E., Yanagida, T., Ikebe, M., 2002. Class VI myosin moves processively along actin filaments backward with large steps. Biochem. Biophys. Res. Commun. 290, 311-317.
Noguchi, T., Lenartowska, M., Miller, K. G., 2006. Myosin VI stabilizes an actin network during Drosophila spermatid individualization. Mol. Biol. Cell 17, 2559-2571.
Noselli, S., Agnes, F., 1999. Roles of the JNK signaling pathway in Drosophila morphogenesis. Curr. Opin. Genet. Dev. 9, 466-472.
Noselli, S., 2002. Drosophila, actin and videotape -- new insights in wound healing. Nat. Cell Biol. 4, E251-253.
Park, H., Ramamurthy, B., Travaglia, M., Safer, D., Chen, L. Q., Franzini-Armstrong, C., Selvin, P. R., Sweeney, H. L., 2006. Full-length myosin VI dimerizes and moves processively along actin filaments upon monomer clustering. Mol. Cell 21, 331-336.
Petritsch, C., Tavosanis, G., Turck, C. W., Jan, L. Y., Jan, Y. N., 2003. The Drosophila myosin VI Jaguar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. Dev. Cell 4, 273-281.
Riesgo-Escovar, J. R., Hafen, E., 1997. Drosophila Jun kinase regulates expression of Decapentaplegic via the ETS-domain protein Aop and the AP-1 transcription factor DJun during dorsal closure. Genes Dev. 11, 1717-1727.
Rock, R. S., Rice, S. E., Wells, A. L., Purcell, T. J., Spudich, J. A., Sweeney, H. L., 2001. Myosin VI is a processive motor with a large step size. Proc. Natl. Acad. Sci. U S A 98, 13655-13659.
Rogat, A. D., Miller, K. G., 2002. A role for myosin VI in actin dynamics at sites of membrane remodeling during Drosophila spermatogenesis. J. Cell Sci. 115, 4855-4865.
Schock, F., Perrimon, N., 2002. Cellular processes associated with germ band retraction in Drosophila. Dev. Biol. 248, 29-39.
Steinberg, M. S., 1978. Cell-cell recognition in multicellular assembly: levels of specificity. Symp. Soc. Exp. Biol. 32, 25-49.
Sweeney, H. L., Houdusse, A., 2007. What can myosin VI do in cells? Curr. Opin. Cell Biol. 19, 57-66.
Takahashi, K., Nakanishi, H., Miyahara, M., Mandai, K., Satoh, K., Satoh, A., Nishioka, H., Aoki, J., Nomoto, A., Mizoguchi, A., Takai, Y., 1999. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. J. Cell Biol. 145, 539-549.
Takahashi, M., Takahashi, F., Ui-Tei, K., Kojima, T., Saigo, K., 2005. Requirements of genetic interactions between Src42A, armadillo and shotgun, a gene encoding E-cadherin, for normal development in Drosophila. Development 132, 2547-2559.
Tateno, M., Nishida, Y., Adachi-Yamada, T., 2000. Regulation of JNK by Src during Drosophila development. Science 287, 324-327.
Van Aelst, L., Symons, M., 2002. Role of Rho family GTPases in epithelial morphogenesis. Genes Dev. 16, 1032-1054.
Verkhusha, V. V., Tsukita, S., Oda, H., 1999. Actin dynamics in lamellipodia of migrating border cells in the Drosophila ovary revealed by a GFP-actin fusion protein. FEBS Lett. 445, 395-401.
Wei, S. Y., Escudero, L. M., Yu, F., Chang, L. H., Chen, L. Y., Ho, Y. H., Lin, C. M., Chou, C. S., Chia, W., Modolell, J., Hsu, J. C., 2005. Echinoid is a component of adherens junctions that cooperates with DE-Cadherin to mediate cell adhesion. Dev. Cell 8, 493-504.
Wells, A. L., Lin, A. W., Chen, L. Q., Safer, D., Cain, S. M., Hasson, T., Carragher, B. O., Milligan, R. A., Sweeney, H. L., 1999. Myosin VI is an actin-based motor that moves backwards. Nature 401, 505-508.
Wodarz, A., Hinz, U., Engelbert, M., Knust, E., 1995. Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 82, 67-76.
Woolner, S., Jacinto, A., Martin, P., 2005. The small GTPase Rac plays multiple roles in epithelial sheet fusion--dynamic studies of Drosophila dorsal closure. Dev. Biol. 282, 163-173.
Woolner, S., Martin, P., 2006. Embryo morphogenesis and the role of the actin cytoskeleton. Advances in Molecular and Cell Biology 37, pp251-283.
Young, P. E., Richman, A. M., Ketchum, A. S., Kiehart, D. P., 1993. Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. Genes Dev. 7, 29-41.
Zecchini, V., Brennan, K., Martinez-Arias, A., 1999. An activity of Notch regulates JNK signalling and affects dorsal closure in Drosophila. Curr. Biol. 9, 460-469.