PUBLICATION

The evolutionally conserved activity of Dapper2 in antagonizing TGF-beta signaling

Authors
Su, Y., Zhang, L., Gao, X., Meng, F., Wen, J., Zhou, H., Meng, A., and Chen, Y.G.
ID
ZDB-PUB-070203-3
Date
2007
Source
FASEB journal : official publication of the Federation of American Societies for Experimental Biology   21(3): 682-690 (Journal)
Registered Authors
Meng, Anming, Meng, Fanwei, Su, Ying
Keywords
receptor degradation, embryonic expression
MeSH Terms
  • Animals
  • Carrier Proteins/pharmacology*
  • Conserved Sequence/physiology*
  • Evolution, Molecular
  • Mice
  • Signal Transduction/drug effects*
  • Signal Transduction/physiology
  • Transforming Growth Factor beta/antagonists & inhibitors*
  • Transforming Growth Factor beta/physiology
  • Zebrafish
PubMed
17197390 Full text @ FASEB J.
Abstract
Dapper1 and Dapper2, two divergent members of the Dapper family, have been suggested to modulate Wnt and TGF-beta/Nodal signaling in Xenopus and zebrafish. To get a better understanding of Dapper function in mammals, we have cloned the mouse ortholog of zebrafish Dapper2, mDpr2 and investigated its function in regulating TGF-beta signaling activity. Here, we showed that, like zebrafish Dapper2, overexpression of mDpr2 inhibited the TGF-beta-induced expression of the Smad-responsive reporters and targeted TGF-beta type I receptor ALK5 for degradation in mammalian cells. Overexpression of mDpr2 in the zebrafish embryos led to a decrease in expression of the mesoderm marker no tail and goosecoid at the shield stage and eye fusion later, implying that mDpr2 may have an intrinsic in vivo activity similar to fish Dapper2 activity. The expression of mDpr2 was detected throughout the epiblast around the onset of gastrulation and in somites, the neural tube and gut at later stages in mouse embryos, implying a role in early embryonic development. Our data indicate that the function of Dpr2 as a negative regulator of the TGF-beta/Nodal signal pathway is evolutionally conserved, at least in part, in fish and mammals.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping