A role for Tbx5 in proepicardial cell migration during cardiogenesis.
Transcriptional regulatory cascades during epicardial and coronary vascular development from proepicardial progenitor cells remain to be defined. We have used immunohistochemistry of human embryonic tissues to demonstrate that the TBX5 transcription factor is expressed not only in the myocardium, but also throughout the embryonic epicardium and coronary vasculature. TBX5 is not expressed in other human fetal vascular beds. Furthermore, immunohistochemical analyses of human embryonic tissues reveals that unlike their epicardial counterparts, delaminating epicardial-derived cells do not express TBX5 as they migrate through the subepicardium before undergoing epithelial-mesenchymal transformation required for coronary vasculogenesis. In the chick, Tbx5 is expressed in the embryonic proepicardial organ (PEO), which is composed of the epicardial and coronary vascular progenitor cells. Retrovirus-mediated overexpression of human TBX5 inhibits cell incorporation of infected proepicardial cells into the nascent chick epicardium and coronary vasculature. TBX5 overexpression as well as antisense-mediated knockdown of chick Tbx5 produce a cell-autonomous defect in the PEO that prevents proepicardial cell migration. Thus, both increasing and decreasing Tbx5 dosage impairs development of the proepicardium. Culture of explanted PEOs demonstrates that untreated chick proepicardial cells downregulate Tbx5 expression during cell migration. Therefore, we propose that Tbx5 participates in regulation of proepicardial cell migration, a critical event in the establishment of the epicardium and coronary vasculature.
Hatcher
Cathy J
CJ
Molecular Cardiology Laboratory, Greenberg Cardiology Division, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
Diman
Nata Y S-G
NY
Kim
Min-Su
MS
Pennisi
David
D
Song
Yan
Y
Goldstein
Marsha M
MM
Mikawa
Takashi
T
Basson
Craig T
CT
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D003331:Coronary Vessels / Q000196:embryology / Q000378:metabolism; D004285:Dogs; D018628:Gene Dosage; D005865:Gestational Age; D006321:Heart / Q000196:embryology*; D006801:Humans; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D010496:Pericardium / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D029961:Zebrafish Proteins / Q000235:genetics
D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C420984:TBX20 protein, human; C420983:Tbx18 protein, mouse; C486013:Tbx20 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C486011:tbx18 protein, zebrafish; C486014:tbx20 protein, zebrafish