Abstract

Activin and nodal family members of the TGF-Beta superfamily have been shown to initiate the fonnation of mesoderm in na?ve, isolated animal cap explants, and thereby mimicking the function of Spemann's organizer. Therefore, in the past, significant efforts have been made to decipher the molecular mechanisms behind activin/nodal signaling, with the result that we learned much about the basic framework of activin/nodal signaling. However, important unanswered questions remain. For instance, we still know very little about the target genes regulated by these factors. Such knowledge is required in order to fully understand the downstream events. Recently, we also came to the realization that, in addition to the canonical TGF- Beta signaling pathway, other, non-canonical pathways mediating activin/nodal signaling may exist. Demonstration of the existence of such a pathway and providing details on how it may function is obviously crucial to discovering how these members of the TGF-Beta superfamily influence germ layer development. The goal of this research project is to provide a better understanding of activin/nodal signaling in order to elucidate not only mechanisms of mesoderm induction but to provide general knowledge of TGF-beta3 signaling as well.
Specific aims of this proposal are:
Aim 1 : To identify activin/nodal target genes and characterize the gene function.
Aim 2 : To investigate the existence of FoxHi (Fast)-independent activin/nodal signaling.
Aim 3 : To determine the Smad4-independent activin/nodal signaling

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD029507-12
Application #
6640347
Study Section
Special Emphasis Panel (ZRG1-CDF-4 (02))
Program Officer
Klein, Steven
Project Start
1992-08-01
Project End
2007-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
12
Fiscal Year
2003
Total Cost
$333,575
Indirect Cost

  Institution

Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Hayata, Tadayoshi; Blitz, Ira L; Iwata, Nahoko et al. (2009) Identification of embryonic pancreatic genes using Xenopus DNA microarrays. Dev Dyn 238:1455-66
Ogata, Souichi; Morokuma, Junji; Hayata, Tadayoshi et al. (2007) TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis. Genes Dev 21:1817-31
Yao, Li-Chin; Blitz, Ira L; Peiffer, Daniel A et al. (2006) Schnurri transcription factors from Drosophila and vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism. Development 133:4025-34
Li, Shuzhao; Shin, Yongchol; Cho, Ken W Y et al. (2006) The Xfeb gene is directly upregulated by Zic1 during early neural development. Dev Dyn 235:2817-27
Koide, Tetsuya; Hayata, Tadayoshi; Cho, Ken W Y (2006) Negative regulation of Hedgehog signaling by the cholesterogenic enzyme 7-dehydrocholesterol reductase. Development 133:2395-405
Koide, Tetsuya; Hayata, Tadayoshi; Cho, Ken W Y (2005) Xenopus as a model system to study transcriptional regulatory networks. Proc Natl Acad Sci U S A 102:4943-8
Shin, Yongchol; Kitayama, Atsushi; Koide, Tetsuya et al. (2005) Identification of neural genes using Xenopus DNA microarrays. Dev Dyn 232:432-44
Arima, Kayo; Shiotsugu, Jason; Niu, Rong et al. (2005) Global analysis of RAR-responsive genes in the Xenopus neurula using cDNA microarrays. Dev Dyn 232:414-31
Peiffer, Daniel A; Von Bubnoff, Andreas; Shin, Yongchol et al. (2005) A Xenopus DNA microarray approach to identify novel direct BMP target genes involved in early embryonic development. Dev Dyn 232:445-56
von Bubnoff, Andreas; Peiffer, Daniel A; Blitz, Ira L et al. (2005) Phylogenetic footprinting and genome scanning identify vertebrate BMP response elements and new target genes. Dev Biol 281:210-26

Showing the most recent 10 out of 22 publications