title: Arid3b is essential for second heart field cell deployment and heart patterning.
abstract: Arid3b, a member of the conserved ARID family of transcription factors, is essential for mouse embryonic development but its precise roles are poorly understood. Here, we show that Arid3b is expressed in the myocardium of the tubular heart and in second heart field progenitors. Arid3b-deficient embryos show cardiac abnormalities, including a notable shortening of the poles, absence of myocardial differentiation and altered patterning of the atrioventricular canal, which also lacks epithelial-to-mesenchymal transition. Proliferation and death of progenitors as well as early patterning of the heart appear normal. However, DiI labelling of second heart field progenitors revealed a defect in the addition of cells to the heart. RNA microarray analysis uncovered a set of differentially expressed genes in Arid3b-deficient tissues, including Bhlhb2, a regulator of cardiomyocyte differentiation, and Lims2, a gene involved in cell migration. Arid3b is thus required for heart development by regulating the motility and differentiation of heart progenitors. These findings identify Arid3b as a candidate gene involved in the aetiology of human congenital malformations.
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Uribe
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain.
authors.forename: Claudio
authors.initials: C
authors.lastname: Badía-Careaga
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain.
authors.forename: Jesús C
authors.initials: JC
authors.lastname: Casanova
authors.affiliation: Departamento de Biología Experimental, Facultad de Ciencias Experimentales, Universidad de Jaén, CU Las Lagunillas, Jáen 23071, Spain.
authors.forename: Jorge N
authors.initials: JN
authors.lastname: Domínguez
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: de la Pompa
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología (CSIC), Darwin, 3, Madrid 28049, Spain jjsanz@cnb.csic.es.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Sanz-Ezquerro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007120:Immunochemistry; D017403:In Situ Hybridization; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; C510769:Arid3b protein, mouse; C491539:Bhlhe40 protein, mouse; C490234:Lims2 protein, mouse
keywords: AVC explant; Arid3b; Cell motility; DiI labelling; Heart development; Mouse; Second heart field; Transcription factor