Abstract
Retinoic acid (RA) is an important signaling molecule in the development of the endoderm and an important molecule in protocols used to generate endodermal cell types from stem cells. In this review, we describe the RA signaling pathway and its role in the patterning and specification of the extra embryonic endoderm and different endodermal organs. The formation of endoderm is an ancient evolutionary feature and RA signaling appears to have coevolved with the vertebrate lineage. Towards that end, we describe how RA participates in many regulatory networks required for the formation of extraembryonic structures as well as the organs of the embryo proper.
Highlights
Retinoic acid (RA) signaling is one of the fundamental regulatory pathways in the development of vertebrates with roles in the differentiation and patterning of lineages from all three germ layers [1,2]J
A significant role for RA signaling in the development of endoderm might appear somewhat surprising because endoderm is a germ layer of all multi-layered embryos, whereas the RA signaling system has often been described as a signaling system that has arisen during chordate evolution [3,4]
RA signaling is required for many early developmental events, there is no evidence that it plays a role in endodermal differentiation in vivo
Summary
Retinoic acid (RA) signaling is one of the fundamental regulatory pathways in the development of vertebrates with roles in the differentiation and patterning of lineages from all three germ layers [1,2]. There is evidence that homologues of enzymes and receptors necessary for RA signaling exist in different invertebrates [5,6,7], but it is still not clear as to whether or not these homologues function in an analogous manner If they have alternate functions, retinoic acid signaling may be an adaption that occurred during evolution and unique to the chordates. The endoderm in vertebrates has evolved a number of novel innovations, including the generation of unique endoderm-derived organs and the formation of an extraembryonic endoderm It is in the development of these novel endoderm features that retinoic acid signaling is clearly required
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