Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ydbio.2004.05.024
Title: Tbx5 and Tbx4 transcription factors interact with a new chicken PDZ-LIM protein in limb and heart development
Authors: Krause, A
Zacharias, W
Camarata, T
Linkhart, B
Law, E 
Lischke, A
Miljan, E
Simon, HG
Keywords: Science & Technology
Life Sciences & Biomedicine
Developmental Biology
limb development
cardiac development
pattern formation
protein interaction
Tbx4
Tbx5
LMP-4
yeast two-hybrid
GST co-precipitation
in situ hybridization
T-BOX GENES
HOLT-ORAM-SYNDROME
DOMAIN PROTEIN
ARTERIAL POLE
KINASE-C
IDENTITY
EXPRESSION
MOUSE
SPECIFICATION
ROLES
Issue Date: 1-Sep-2004
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation: Krause, A, Zacharias, W, Camarata, T, Linkhart, B, Law, E, Lischke, A, Miljan, E, Simon, HG (2004-09-01). Tbx5 and Tbx4 transcription factors interact with a new chicken PDZ-LIM protein in limb and heart development. DEVELOPMENTAL BIOLOGY 273 (1) : 106-120. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ydbio.2004.05.024
Abstract: 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 co-localization 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. © 2004 Elsevier Inc. All rights reserved.
Source Title: DEVELOPMENTAL BIOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/228859
ISSN: 00121606
1095564X
DOI: 10.1016/j.ydbio.2004.05.024
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