Pitx2-mediated cardiac outflow tract remodeling.
BACKGROUND
Heart morphogenesis involves sequential anatomical changes from a linear tube of a single channel peristaltic pump to a four-chamber structure with two channels controlled by one-way valves. The developing heart undergoes continuous remodeling, including septation.


RESULTS
Pitx2-null mice are characterized by cardiac septational defects of the atria, ventricles, and outflow tract. Pitx2-null mice also exhibited a short outflow tract, including unseptated conus and deformed endocardial cushions. Cushions were characterized with a jelly-like structure, rather than the distinct membrane-looking leaflets, indicating that endothelial mesenchymal transition was impaired in Pitx2(-/-) embryos. Mesoderm cells from the branchial arches and neural crest cells from the otic region contribute to the development of the endocardial cushions, and both were reduced in number. Members of the Fgf and Bmp families exhibited altered expression levels in the mutants.


CONCLUSIONS
We suggest that Pitx2 is involved in the cardiac outflow tract septation by promoting and/or maintaining the number and the remodeling process of the mesoderm progenitor cells. Pitx2 influences the expression of transcription factors and signaling molecules involved in the differentiation of the cushion mesenchyme during heart development.
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
Hsiao-Yen
HY
Ma
Jun
J
Xu
Diana
D
Eng
Michael K
MK
Gross
Chrissa
C
Kioussi
D000818:Animals; D016923:Cell Death / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D004694:Endocardial Cushion Defects / Q000235:genetics; D054089:Endocardial Cushions / Q000196:embryology / Q000378:metabolism; D004699:Endocardium / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology* / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2