Expression and regulation of the retinoic acid synthetic enzyme RALDH-2 in the embryonic chicken wing

Retinaldehyde dehydrogenase type 2 (RALDH-2) is a major retinoic acid (RA) generating enzyme in the embryo. Here, we report immunolocalization of this enzyme (RALDH-2-IR) in the developing wings of stage 17-30 chicken embryos. RALDH-2-IR is located in the area of the presumptive muscle masses, although it is not colocalized with developing muscle cells. RALDH-2-IR is located in tendon precursor cells and may be present in muscular connective tissue. We show that motor neurons and blood vessels, tissues showing RALDH-2-IR as they enter the limb, are capable of synthesizing and releasing RA in culture. RALDH-2-IR in the limb mesenchyme is under the control of both the vasculature and the motor innervation; it is decreased with denervation and increased with hypervascularization. RALDH-2-IR is present in the motor neuron pool of the brachial spinal cord, but this expression pattern is apparently not under the control of limb target tissues, RA in the periphery, or somitic factors. RA is known to be a potent inducer of cellular differentiation; we propose that locally synthesized RA may be involved in aspects of wing tissue specification, including cartilage condensation and outgrowth, skeletal muscle differentiation, and recruitment of smooth muscle cells to the vasculature.