Early retinoic acid signaling organizes the body axis and defines domains for the forelimb and eye

All-trans retinoic acid (ATRA) plays a crucial role in early vertebrate development by regulating gene expression. It influences the formation of the body axis and defines specific regions for the development of forelimbs and eyes. ATRA is first generated in mouse embryos at stage E7.5, and it performs three essential functions: controlling hindbrain and spinal cord patterning, repressing Fgf8 to allow proper somitogenesis and heart morphogenesis, and stimulating optic vesicle invagination for eye formation. Genetic studies involving knockouts of ATRA-generating enzymes have provided insights into the normal functions of ATRA during embryogenesis, revealing its specific roles in tissue development.

• 1
  Early-generated ATRA performs three essential functions: (1) activation of genes that control hindbrain and spinal cord patterning; (2) repression of Fgf8 in the heart field and caudal progenitors; and (3) actions that stimulate invagination of the optic vesicle to form the optic cup.
• 2
  ATRA signaling in mouse embryos is first observed at E7.5, localized to a region spanning from the posterior hindbrain to the junction between the trunk and caudal epiblast that contains neuromesodermal progenitors.
• 3
  Complete loss of ATRA activity in Aldh1a2 knockouts results in failure to initiate forelimb development at E8.5.