title: Foxc2 in pharyngeal arch mesenchyme is important for aortic arch artery remodelling and ventricular septum formation.
abstract: The forkhead box C2 (Foxc2) protein is a member of the forkhead/winged helix transcription factor family and plays an essential role in cardiovascular development. Previous studies showed that Foxc2 null mouse embryos die during midgestation or just after birth with severe cardiovascular defects, including interruption, coarctation of the aortic arch and ventricular septal defects. These are also seen in human congenital heart disease. However, the tissue specific role of Foxc2 in aortic arch remodelling is not yet fully understood. Here we show that Foxc2 is expressed in a restricted pattern in several cell populations, including the mesenchyme and endothelium of pharyngeal arch arteries, which are important for cardiovascular development. In this study, we use a conditional knockout approach to examine the tissue specific role of Foxc2 in aortic arch remodelling. We demonstrate that mouse embryos lacking Foxc2 in Nkx2.5-expressing mesenchyme and endothelium of pharyngeal arch arteries display aortic arch interruption type B and ventricular septal defects. In contrast, conditional deletion of Foxc2 in Tie2-expressing endothelial cells does not result in aortic arch or ventricular septal defects, but does result in embryonic lethality due to peripheral oedema. Our data therefore provide for a detailed understanding of the role of mesenchymal Foxc2 in aortic arch remodelling and in the development of ventricular septum.
authors: Department of Biochemistry, Hamamatsu University School of Medicine.
authors: Mohammad Khaja Mafij
authors: MK
authors: Uddin
authors: Wataru
authors: W
authors: Kimura
authors: Tomoyuki
authors: T
authors: Ishikura
authors: Haruhiko
authors: H
authors: Koseki
authors: Nobuaki
authors: N
authors: Yoshida
authors: Mohammad Johirul
authors: MJ
authors: Islam
authors: Mohammed Badrul
authors: MB
authors: Amin
authors: Kasumi
authors: K
authors: Nakamura
authors: Yi-Xin
authors: YX
authors: Wu
authors: Eiji
authors: E
authors: Sato
authors: Kazushi
authors: K
authors: Aoto
authors: Naoyuki
authors: N
authors: Miura
mesh_terms: D000483:Alleles; D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology* / Q000378:metabolism*; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism*; D018376:Cardiovascular Abnormalities / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005838:Genotype; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D054088:Ventricular Septum / Q000196:embryology / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein; D042787:Receptor, TIE-2; C079086:Tek protein, mouse