Retinoic acid and limb bud development

Limb bud development is a good system in which to study the role of retinoids as morphogens. Retinoids are natural and synthetic compounds related to retinol and retinoic acid. Retinoic acid is formed by the oxidation of retinol (see Section 2.4.1), and both retinoic acid and the related metabolite 3,4-didehyd-roretinoic acid are present in the normal limb buds of chick embryos (Scholfield, Rowe Brickell, 1992), 

Retinoic acid is a hydrophobic molecule able to diffuse across the plasmalemma. Its mechanism of action is similar to that of the steroid hormones (see Section 10.1). It binds to nuclear receptors, which act as transcriptional activators. Two families of retinoic acid and retinoid receptors, RAR and RXR, have been identified in mammals and domestic fowl. The RAR family includes RAR-a, RAR-j8, RAR-y and RAR-d, and the RXR includes RXR-a, RXR-p and RXR-y (Smith Eichele, 1991 Gudas, 1994). Each gene is able to form multiple transcripts, probably by alternative splicing for example, RAR-y forms seven transcripts, and three (3.2, 3.4 and 4.6 kb). 

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