Function of RARγ and RARα2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis

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Abstract
Avian embryogenesis requires retinoid receptor activation by the vitamin A active form, retinoic acid (RA), during neurulation. We conducted loss‐of‐function analysis in quail embryos by nutritional deprivation of RA and by blocking generation of retinoid receptors. Here we identify a distinct role for RARα2 in cardiac inflow tract morphogenesis and for RARγ in cardiac left/right orientation and looping morphogenesis. Blocking normal embryos with antisense oligonucleotides to RARα2 or RXRα diminishes GATA‐4 transcripts, while blocking RARγ or RXRα diminishes nodal and Pitx2 transcripts; the expression of these genes in the heart forming region resembles that of the vitamin A‐deficient embryo. Blocking the function of RARγ, RARα2, and RXRα recapitulates the complete vitamin A‐deficient phenotype. RARγ is the most potent mediator of the retinoid signal at this time of development. Our studies provide strong evidence that critical RA‐requiring developmental events in the early avian embryo are regulated by means of distinct retinoid receptor signaling pathways. Developmental Dynamics 228:697–708, 2003.