Retinoic acid, RARs and early development

Vitamin A is crucial for embryonic development and adult health, with retinoic acid (RA) being a key metabolite. RA influences gene expression by binding to nuclear RA receptors (RARs), a process known as RA signaling. This signaling is vital for the development of various organs and tissues in the embryo. RA is synthesized from retinol in a two-step process involving enzymes like RDH10 and ALDH1A. To prevent excessive RA, enzymes like CYP26 degrade RA, ensuring tissue-specific RA signaling during early development. Genetic loss-of-function studies, such as RAR knockouts, have been crucial in determining RA signaling's functions. These studies revealed that RA signaling is essential for the early development of various organs and tissues.

• 1
  RA signaling is required for normal early development of many organs and tissues, including the hindbrain, posterior body axis, somites, spinal cord, forelimbs, heart, and eye.
• 2
  RA signaling represses caudal Fgf8; thus excessive caudal FGF8 signaling evidently interferes with somitogenesis when Fgf8 is expressed too far anteriorly.
• 3
  In mouse embryos undergoing the late stage of gastrulation, RA synthesis begins upon initial expression of Rdh10 and Aldh1a2 in the presomitic mesoderm.