[4] In adult tissues, the activity of endogenous retinoic acid appears limited to immune function[2] and male fertility.

High oral doses of preformed vitamin A (retinyl palmitate), and all-trans-retinoic acid itself, also have teratogenic potential by this same mechanism.

[3][4] The concentration of retinoic acid is tightly controlled and governs activation of the retinoid nuclear receptor pathway.

[10] In adults, retinoic acid is only detected at physiologically relevant levels in the testes, pancreas and immune tissues.

These types of studies strongly support the normal roles of retinoids in patterning vertebrate embryogenesis through the Hox genes.

The hindbrain, which later differentiates into the brain stem, serves as a major signaling center defining the border of the head and trunk.

Genetic loss-of-function studies in mouse and zebrafish embryos that eliminate retinoic acid synthesis or retinoic acid receptors (RARs) have revealed abnormal development of the somites, forelimb buds, heart, hindbrain, spinal cord, eye, forebrain basal ganglia, kidney, foregut endoderm, etc.