期刊
DEVELOPMENTAL BIOLOGY
卷 273, 期 1, 页码 106-120出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2004.05.024
关键词
limb development; cardiac development; pattern formation; protein interaction; Tbx4; Tbx5; LMP-4; yeast two-hybrid; GST co-precipitation; in situ hybridization
资金
- NIEHS NIH HHS [ES012725-01] Funding Source: Medline
The T-domain transcription factors, Tbx5 and Tbx4, play important roles in vertebrate limb and heart development. To identify interacting and potential Tbx-regulating proteins, we performed a yeast two-hybrid screen with the C-terminal domain of Tbx5 as bait. We identified a new PDZ-LIM protein composed of one N-terminal PDZ and three C-terminal LIM domains, which we named chicken LMP-4. Among the Tbx2, 3, 4, 5 subfamily, we observed exclusive interaction with Tbx5 and Tbx4 proteins. Tbx3 nor Tbx2 can substitute for LMP-4 binding. While chicken LMP-4 associates with Tbx5 or Tbx4, it uses distinct LIM domains to bind to the individual proteins. Subcellular colocalization of LMP-4 and Tbx proteins supports the protein interaction and reveals interference of LMP-4 with Tbx protein distribution, tethering the transcription factors to the cytoskeleton. The protein-protein interaction indicates regulation of Tbx function at the level of transcription factor nuclear localization. During chicken limb and heart development, Tbx5/LMP-4 and Tbx4/LMP-4 are tightly co-expressed in a temporal and spatial manner, suggesting that they operate in the same pathway. Surprisingly, chicken LMP-4 expression domains outside those of Tbx5 in the heart led to the discovery of Tbx4 expression in the outflow tract and the right ventricle of this organ. The Tbx4-expressing cells coincide with those of the recently discovered secondary anterior heart-forming field. The discrete posterior or anterior expression domains in the heart and the exclusive fore- or hindlimb expression of Tbx5 and Tbx4, respectively, suggest common pathways in the heart and limbs. The identification of a new Tbx5/4-specific binding factor further suggests a novel mechanism for Tbx transcription factor regulation in development and disease. (C) 2004 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据