Prof

Hidetoshi Saiga

e-mail

saiga-hidetoshi@tmu.ac.jp

Asc Prof

Kimiko Fukuda

e-mail

kokko@tmu.ac.jp

Exploring the basic developmental program of chordates

Ascidians, lower invertebrate chordates, occupy a peculiar position in the animal phylogeny. A fertilized egg of the ascidians develops into a tadpole-shaped larva in a day, which in turn metamorphoses into the sessile adult form within a couple of days. The larval development of ascidians appears quite simple but shares characteristics of the morphogenesis in the chordate development. It is well known that developmental genes, which are relatively small groups of genes encoding transcription factors or signal transduction molecules, play a critical role in animal development from studies on "model animals". It is, however, largely unknown what the genes actually do in the development of various animals other than the model animals. We are studying the expression, function and regulatory mechanisms of developmental genes in the ascidian development to understand the molecular mechanisms underlying its morphogenesis. Throughout these studies, we are trying to understand what is the basic developmental program of chordates, how it was established and how it has evolved in the lineages to ascidians and other chordates.

Mechanisms of endodermal development and patterning in vertebrate animals

The endoderm becomes the epithelium lining the gastrointestinal tract and the respiratory organs, and research on the molecular mechanisms of its differentiation has made slower progress than research on tissues derived from other germ layers (muscle or nerve). We have conducted research on when and where the endoderm develops, and the molecular mechanisms of endoderm establishment. In addition, although the characteristics of the endoderm are initially almost uniform, it is differentiated into entirely different organs along the anterior-posterior axis, the left-right axis or the dorsoventral axis. We have also conducted studies to elucidate when and how the endodermal patterning occurs.

Basic developmental program of digestive tract formation in chordates

In ascidians, the digestive tract forms from an undifferentiated endodermal cell mass ventrally located in the tadpole trunk. In chick embryos, the foregut or hindgut is formed from a sheet of the endodermal tissue. The digestive tract formation at the initial stage looks quite different between the two animals groups, but in later stages, the esophagus, stomach and gut develop with similar locations along the anterior-posterior axis in the digestive tract. In addition, some developmental genes such as Sox, Cdx and Hox exhibit shared expression patterns along the anterior-posterior axis. We are interested in elucidating a basic developmental program of digestive tract formation, using the ascidian Ciona intestinalis with a wealth of genomic information and chick embryos with a wealth of experimental embryological information as model systems.

Related Links

Recent Publications

1. Ikuta, T., Satoh, N. and Saiga, H. (2010) Limited functions of Hox genes in the larval development of the ascidian, Ciona intestinalis. Development, 137, 1505-1513.
2. Kobayashi, M., Takatori, N., Nakajima, Y., Kumano, G., Nishida, H. and Saiga, H. (2010) Spatial and temporal expression of two transcriptional isoforms of Lhx3, a LIM class homeobox gene, during embryogenesis of two phylogenetically remote ascidians, Halocynthia roretzi and Ciona intestinalis. Gene Exp. Patterns, 10, 98-104.
3. Ikuta, T., Miyamoto, N., Saito Y., Wada, H., Satoh, N. and Saiga, H. (2009) Ambulacrarian prototypical Hox and ParaHox gene complements of the indirect-developing hemichordate Balanoglossus simodensis. Dev. Genes and Evol. 219, 383-389.
4. Yasuoka, Y., Kobayashi, M., Kurokawa, D., Akasaka, K., Saiga, H. and Taira, M. (2009) Evolutionary roots of blastoporal expression and �eorganizer�f activity of the vertebrate gastrula organizer gene lhx1 and its ancient metazoan paralog lhx3. Development 136, 2005-2014.
5. Matsuura, K., Katsumoto, K., Fukuda, K., Kume, K. and Kume. S. (2009) Conserved origin of the ventral pancreas in chicken. Mech Dev. 126, 817-827.
6. Katsumoto, K., Fukuda, K., Kimura, W., Shimamura, K., Yasugi, S. and Kume, S. (2009) Origin of pancreatic precursors in the chick embryo and the mechanism of endoderm regionalization. Mec. Dev. 126, 539-551
7. Takatori, N., Butts, T., Candiani, S., Pestarino, M., Ferrier, D.E.K., Saiga, H. and Holland, P.W.H. (2008) Comprehensive survey and classification of homeobox genes in the genome of amphioxus, Branchiostoma floridae. Dev. Genes Evol. 218, 570-590.
8. Yoshida, K. and Saiga, H. (2008) Left-right asymmetric expression of Pitx is regulated by the asymmetric Nodal signaling through an intronic enhancer in Ciona intestinalis. Dev. Genes Evol. 218, 353-360.
9. Holland, L.Z., Albalat, R., Azumi,K., Benito-Gutiérrez, E., Blow, M.J., Bronner-Fraser, M., Brunet, F., Butts, T., Candiani, S., Dishaw, L.J., Ferrier, D.E.K., Garcia-Fernàndez, J., Gibson-Brown, J.J., Gissi, C., Godzik, A., Hallböök, F., Hirose, D., Hosomichi, K., Ikuta, T., Inoko, H., Kasahara, M., Kasamatsu, J., Kawashima, T., Kimura, A., Kobayashi, M., Kozmik, Z., Kubokawa,K., Laudet,V., Litman, G.W., McHardy, A.C., Meulemans, D., Nonaka, M., Olinski, R.P., Pancer, Z., Pennacchio, L.A., Pestarino, M., Rast, J.P., Rigoutsos, I., Robinson-Rechavi, M., Roch, G., Saiga, H., Sasakura, Y., Satake, M., Satou, Y., Schubert, M., Sherwood, N., Shiina, T., Takatori, N,, Tello, J., Vopalensky, P., Wada, S., Xu, A., Ye, Y., Yoshida, K., Yoshizaki, F., Jr-Kai, Y., Zhang, Q., Zmasek, C.M., Putnam, N.H., Rokhsar, D.S., Satoh, N. and Holland, P.W.H.(2008) The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res. 18, 1100-1111.
10. Takatori, N. and Saiga, H. (2008) Evolution of CUT class homeobox genes: insights from the genome of the amphioxus, Branchiostoma floridae. Int. J. Dev. Biol. 52, 969-977.
11. Ikuta, T. and Saiga, H. (2007) Dynamic change in the expression of developmental genes in the ascidian central nervous system: revisit to the tripartite model and the origin of the midbrain-hindbrain boundary region. Dev. Biol. 312, 631-643.
12. Takatori, N., Wada, S. and Saiga, H. (2007) Regionalization of the tail-tip epidermis requires inductive influence from vegetal cells and FGF signaling in the development of an ascidian, Halocynthia roretzi. Zool. Sci. 24, 441-448.
13. Kimura, W., Yasugi, S. and Fukuda, K. (2007) Regional specification of the endoderm in the early chick embryo. Dev. Growth & Differ. 49, 365-372.
14. Hojo, M., Takada, I., Kimura, W., Fukuda, K. and Yasugi, S. (2006) Expression patterns of the chicken peroxisome proliferator-activated receptors (PPARs) during the development of the digestive organs. Gene Expression Patterns 6, 171-179.
15. Shin, M., Noji, S., Neubu�Nsser, A. and Yasugi, S. (2006) FGF10 is required for cell proliferation and gland formation in the stomach epithelium of the chicken embryo. Dev. Biol. 294, 11-23.
16. Kimura, W., Yasugi, S., Stern, C. and Fukuda, K. (2006) Fate and plasticity of the endoderm in the early chick embryo. Dev. Biol. 289, 283-295.
17. Oda-Ishii, I., Bertrand, V., Matsuo, I., Lemaire, P. and Saiga, H. (2005) Making very similar embryos with divergent genomes: conservation of regulatory mechanisms of Otx between the ascidians Halocynthia roretzi and Ciona intestinalis. Development 132, 1663-1674.
18. Ikuta T. and Saiga, H. (2005) Organization of Hox genes in ascidians: present, past and future. Dev. Dyn. 233, 382-389
19. Keys, D. N., Lee, B., Di Gregorio, A., Harafuji, N., Detter, J. C., Wang, M., Kahsai, O., Ahn, S., Zhang, C., Doyle, S. A., Satoh, N., Satou, Y., Saiga, H., Christian, A. T., Rokhsar, D. S., Hawkins, T. L., Levine, M. and Richardson, P. M. (2005) A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis. Proc. Natl. Acad. Sci. U.S.A. 102, 679-683.
20. Matsuda, Y., Wakamatsu, Y., Kohyama, J., Okano, H., Fikuda, K. and Yasugi, S. (2005) Notch signaling functions as a binary switch for the determination of glandular and luminal fates of endodermal epithelium during chicken stomach development. Development 132, 2783-2793.
21. Asai, R., Okano, H. and Yasugi, S. (2005) Correlation between Musashi-1 and c-hairy-1 expression and cell proliferation activity in the developing intestine and stomach of both chicken and mouse. Dev. Growth & Differ. 47, 501-510.
22. Hoshino, A., Koide, M., Ono, t. and Yasugi, S. (2005) Sex-specific and left-right asymmetric expression pattern of Bmp7 in the gonad of normal and sex-reversed chicken embryos. Dev. Growth Differ. 47, 65-74.
23. Hojo, M., Takada, I., Kimura, W., Fukuda, K. and Yasugi, S. (2005) Expression patterns of the chicken peroxisome proliferator-activated receptors (PPARs) during the development of the digestive organs. Gene Expression Patterns 6, 171-179.
24. Shin, M., Watanuki, K. and Yasugi, S. (2005) Expression of Fgf10 and Fgf receptors during development of the embryonic chicken stomach. Gene Expression Patterns 5, 511-516.
25. Utsumi, N., Shimojima, Y. and Saiga, H. (2004) Analysis of ascidian Not genes highlights their evolutionarily conserved and derived features of the structure and expression in the development. Dev. Genes Evol. 214, 460-465.
26. Ikuta, T., Yoshida, N., Satoh, N. and Saiga, H. (2004) Ciona intestinalis Hox gene cluster: its dispersed structure and residual colinear expression in development. Proc. Natl. Acad. Sci. U.S.A. 101, 15118-15123.
27. Wada, S., Sudou, N. and Saiga, H. (2004) Roles of Hroth, the ascidian otx gene, in the differentiation of the brain (sensory vesicle) and anterior trunk epidermis in the larval development of Halocynthia roretzi. Mech. Dev. 121, 463-474.
28. Shoguchi, E., Ikuta, T., Yoshizaki, F., Satou, Y., Satoh, N., Asano, K., Saiga, H. and Nishikata, T. (2004) Fluorescent in situ hybridization to ascidian chromosomes. Zool. Sci. 21, 153-157.
29. Toyoda, R., Kasai, A., Sato, S., Wad,a S., Saiga, H., Ikeo, K., Gojobori, T., Numakunai, T., and Yamamoto, H. (2004) Pigment cell lineage-specific expression activity of the ascidian tyrosinase-related gene. Gene 332, 61-69.
30. Hiramatsu, H. and Yasugi, S. (2004) Molecular analysis of the determination of developmental fate in the small Intestinal epithelium in the chicken embryo. Int. J. Dev. Biol. 48: 1141-1148.
31. Oda-Ishii, I. and Saiga, H. (2003) Genomic organization and promoter and transcription regulatory regions for the expression in the anterior brain (sensory vesicle) of Hroth, the otx homologue of the ascidian, Halocynthia roretzi. Dev. Dyn. 227, 104-113.
32. Endo, Y., Nonaka, M., Saiga, H., Kakinuma, Y., Matsushita, A., Takahashi, M., Matsushita, M. and Fujita, T. (2003) Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway traced back to the invertebrate, amphioxus. J. Immunol. 170, 4701-4707.
33. Kobayashi, K., Sawada, K., Yamamoto, H., Wada, S., Saiga, H. and Nishida, H. (2003) Maternal macho-1 is an intrinsic factor that makes cell response to the same FGF signal differ between mesenchyme and notochord induction in ascidian embryos. Development 130, 5179-5190.
34. Wada, S., Tokuoka, M., Shoguchi, E., Kobayashi, K., Di Gregorio, A., Spagnuolo, A., Branno, M., Kohara, Y., Rokhsar, D., Levine, M., Saiga, H., Satoh, N. and Satou, Y. (2003) A genomewide survey of developmentally relevant genes in Ciona intestinalis II. Genes for homeobox transcription factors. Dev. Genes Evol. 213, 222-234.
35. Shimizu, Y., Yamamichi, N., Saitoh, K., Watanabe, A., Ito, M., Yamamichi-Nishina, M., Mizutani, M., Yahagi, N., Suzuki, T., Sasakawa, C., Yasugi, S., Ichinose, M. and Iba, H. (2003). Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach. Oncogene 22, 884-893.
36. Saito, K., Kawaguchi, A., Kashiwagi, S., Yasugi, S., Ogawa, M. and Miyata, T. (2003) Morphological asymmetry in dividing retinal progenitor cells. Dev. Growth & Differ. 45: 219-229.
37. Fukuda, K., Kameda, T., Saitoh, K., Iba, H. and Yasugi, S. (2003) Down-regulation of endodermal Shh is required for gland formation in chicken stomach. Mech. Dev. 120: 801-809.
38. Shin, M., Fukuda, K. and Yasugi, S. (2003) Expression of DDSG1, a novel gene encoding a putative DNA-binding protein in the embryonic chicken nervous system. Mech. Dev. Gene Expression 3, 431-436.
39. Watanuki, K. and Yasugi, S. (2003) Analysis of transcription regulatory regions of embryonic chicken pepsinogen (ECPg) gene. Dev. Dyn. 228: 51-58.
40. Wada, S. and Saiga, H.( 2002) HrzicN, a new Zic family gene of ascidians, plays essential roles in the neural tube and notochord development. Development 129, 5597-5608.
41. Wada, S., Toyoda, R., Yamamoto, H. and Saiga, H. (2002) The ascidian otx gene Hroth activates transcription of a brain specific gene HrTRP. Dev. Dyn. 225, 46-53.
42. Wang, Y., Zhang, P.J., Yasui, K. and Saiga, H.(2002) Expression of Bblhx3, a LIM-homeobox gene, in the development of amphioxus Branchiostoma belcheri tsingtauense. Mech. Dev. 117, 315-319.
43. Dehal, P., Satou, Y., Campbell, R.K., Chapman, J., Degnan, B., De Tomaso, A., Davidson, B., Di Gregorio, A., Gelpke, M., Goodstein, D., Harafuji, N., Hastings, K., Ho, I., Hotta, K., Huang, W., Kawashima, T., Lemaire, P., Martinez, D., Meinertzhagen, I. A., Necula, S., Nonaka, M., Putnam, N., Rash, S., Saiga, H., Satake, M., Terry, A., Yamada, L., Wang H.-G., Awazu A., Azumi K., Boore J., Branno M., Chin-bow S., DeSantis R., Doyle, S., Francino, P., Keys, D., Haga, S., Hayashi, H., Hino, K., Imai, K. S., Inaba, K., Kano, S., Kobayashi, K., Kobayashi, M., Lee, B.-I., Makabe, K.W., Manohar, C., Matassi, G., Medina, M., Mochizuki, Y., Mount, S., Morishita, T., Miura, S., Nakayama, A., Nishizaka, S., Nomoto, H., Ohta, F., Oishi, K., Rigoutsos, I., Sano, M., Sasaki, A., Sasakura, Y., Shoguchi, E., Sin-I, T., Spagnuolo, A., Stainier, D., Suzuki, M.M., Tassy, O., Takatori. N., Tokuoka, M., Yagi, K., Yoshizaki, F., Wada, S., Zhang, C., Hyatt, P.D., Larimer, F., Detter, C., Doggett, N., Glavina, T.,Hawkins, T.,Richardson, P., Lucas, S.,Kohara, Y., Levine, M., Satoh N. and Rokhsar, D. (2002) The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298, 2157-2167.
44. Morokuma, J., Ueno, M., Kawanishi H., Saiga, H. and Nishida, H. (2002) HrNodal, the ascidian nodal-related gene is expressed in the left side epidermis, and lies upstream of HrPitx. Dev. Genes Evol. 212, 439-446.
45. Satoh, G.,Takeuchi, J., Yasui, K., Tagawa, K., Saiga, H., Zhang, P. and Satoh, N.(2002) Amphi-Eomes/Tbr : An amphioxus cognate of vertebrate Eomesodermin and T-Brain1 genes whose expression reveals evolutionarily distinct domain in amphioxus development. J. Exp. Zool. (Mol. Dev. Evol.) 294, 136-145.
46. Satou, Y., Takatori, N., Fujiwara, S., Nishikata, T., Saiga, H., Kusakabe, T. Shin-I, T., Kohara, Y. and Satoh, N.(2002) Ciona intestinalis cDNA projects: expressed sequence tag analyses and gene expression profiles during embryogenesis. Gene 287, 83-96.
47. Yasui, K., Li, G., Wang, Y., Saiga, H., Zhang, P. and Aizawa, S. (2002) ƒÀ-catenin in early development of the lancelet embryo implicating a specific determination of the embryonic polarity. Develop. Growth Differ. 44, 467-475.
48. Fukuda, K. and Yasugi, S. (2002) Versatile roles for sonic hedgehog in gut development. J. Gastroenterol. 37, 239-246.
49. Matsushita, S., Ishii, Y., Scotting, P. J. and Yasugi, S. (2002). The pre-gut endoderm of chick embryos is regionalized by 1.5 days of development. Dev. Dyn. 223, 33-47.
50. Yasugi, E., Uemura, I., Kumagai, T., Nishikawa, Y., Yasugi, S.. and Yuo, A. (2002). Disruption of mitochondria is an early event during dolichyl monophosphate-induced apoptosis in U937 cells.�@Zool. Sci. 19: 7-13.
51. Takeda, J., Tabata, H., Fukuda, K. and Yasugi, S. (2002). The involvement of signal transduction pathway mediated by epidermal growth factor receptor in the differentiation of chicken glandular stomach. Dev. Growth & Differ. 44: 501-508