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RESEARCH PRODUCT

Function of RAR? and RAR?2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis

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description

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. © 2003 Wiley-Liss, Inc.