Retinoic acid synthesis and functions in early embryonic development

Retinoids refer to those chemicals that are structurally or functionally similar to retinol, or vitamin A [1], which is an essential biomolecule for embryonic development and adult body homeostasis. All retinoids retain the polyene hydrophobic tail attached to a cyclic 6-carbon ring. The polyene tail is characterized by the alternating conjugated carbon-carbon double bonds, which makes retinoids light-sensitive. In contrast with other signaling proteins, retinoids have a much lower molecular weight of approximately 300 Da. Given their molecular structures, retinoids are highly oil-soluble and able to diffuse across the cell membrane. Retinoids are involved in cellular growth, apoptosis, immune response, and epithelial growth [2-7] through the interaction with the nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR). During early embryonic development, the major active form of retinoids, all-trans retinoic acid (atRA), regulates germ layer formation, body axis formation, neurogenesis, cardiogenesis, and the development of pancreas, lung, and eye. It is also a critical element for visual function [8]. Because of the wide spectrum of RA functions, the metabolism, regulation, and function of vitamin A have been extensively studied for decades, and here we summarize our current understanding on retinoids metabolic pathways and RA functions during early embryonic development.Vitamin A is a necessary dietary vitamin for the normal development and vision. The critical necessity of vitamin A was hinted as early as 1881 by Nikolai Lunin, who discovered that purified protein, fat, and carbohydrate did not sustain the normal growth of mice, unless the diet was supplemented with milk. Elmer Verner McCollum, then determined in 1917 that the critical component concerned in milk was actually a "fat-soluble factor A", named in contrast to the previously discovered "water-soluble factor B", or vitamin B. These discoveries allowed Carl Edvard Bloch, a Denmark