Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis.
Members of the T-box family of proteins play a fundamental role in patterning the developing vertebrate heart; however, the precise cellular requirements for any one family member and the mechanism by which individual T-box genes function remains largely unknown. In this study, we have investigated the cellular and molecular relationship between two T-box genes, Tbx5 and Tbx20. We demonstrate that blocking Tbx5 or Tbx20 produces phenotypes that display a high degree of similarity, as judged by overall gross morphology, molecular marker analysis and cardiac physiology, implying that the two genes are required for and have non-redundant functions in early heart development. In addition, we demonstrate that although co-expressed, Tbx5 and Tbx20 are not dependent on the expression of one another, but rather have a synergistic role during early heart development. Consistent with this proposal, we show that TBX5 and TBX20 can physically interact and map the interaction domains, and we show a cellular interaction for the two proteins in cardiac development, thus providing the first evidence for direct interaction between members of the T-box gene family.
Brown
Daniel D
DD
Department of Genetics, Fordham Hall, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Martz
Shauna N
SN
Binder
Olav
O
Goetz
Sarah C
SC
Price
Brenda M J
BM
Smith
Jim C
JC
Conlon
Frank L
FL
D000818:Animals; D002452:Cell Count; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006801:Humans; D051379:Mice; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D020825:T-Box Domain Proteins