Hox genes define distinct progenitor sub-domains within the second heart field |
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Authors: | Bertrand Nicolas Roux Marine Ryckebüsch Lucile Niederreither Karen Dollé Pascal Moon Anne Capecchi Mario Zaffran Stéphane |
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Affiliation: | aLaboratoire de Génétique Médicale et Génomique Fonctionnelle, Inserm UMR_S910, Université d'Aix-Marseille, 27 Bd Jean Moulin, 13005 Marseille, France;bDepartment of Nutritional Sciences, Dell Pediatric Research Institute, University of Texas, Austin, TX, USA;cInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U964/Centre National de Recherche Scientifique (CNRS) UMR 1704/Université de Strasbourg, 67404 Illkirch, France;dProgram in Molecular Medicine, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA;eProgram in Molecular Medicine, Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT, USA;fProgram in Molecular Medicine, Department of Human Genetics, University of Utah, Salt Lake City, UT, USA;gHoward Hughes Medical Institute, University of Utah, Salt Lake City, UT, USA |
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Abstract: | Much of the heart, including the atria, right ventricle and outflow tract (OFT) is derived from a progenitor cell population termed the second heart field (SHF) that contributes progressively to the embryonic heart during cardiac looping. Several studies have revealed anterior-posterior patterning of the SHF, since the anterior region (anterior heart field) contributes to right ventricular and OFT myocardium whereas the posterior region gives rise to the atria. We have previously shown that Retinoic Acid (RA) signal participates to this patterning. We now show that Hoxb1, Hoxa1, and Hoxa3, as downstream RA targets, are expressed in distinct sub-domains within the SHF. Our genetic lineage tracing analysis revealed that Hoxb1, Hoxa1 and Hoxa3-expressing cardiac progenitor cells contribute to both atria and the inferior wall of the OFT, which subsequently gives rise to myocardium at the base of pulmonary trunk. By contrast to Hoxb1Cre, the contribution of Hoxa1-enhIII-Cre and Hoxa3Cre-labeled cells is restricted to the distal regions of the OFT suggesting that proximo-distal patterning of the OFT is related to SHF sub-domains characterized by combinatorial Hox genes expression. Manipulation of RA signaling pathways showed that RA is required for the correct deployment of Hox-expressing SHF cells. This report provides new insights into the regulatory gene network in SHF cells contributing to the atria and sub-pulmonary myocardium. |
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Keywords: | Retinoic acid Heart development Mouse Hox genes Cardiac progenitor cells |
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