Abstract
Retinoic acid (RA) signaling is an important regulator of chordate development. RA binds to nuclear RA receptors that control the transcriptional activity of target genes. Controlled local degradation of RA by enzymes of the Cyp26a gene family contributes to the establishment of transient RA signaling gradients that control patterning, cell fate decisions and differentiation. Several steps in the lineage leading to the induction and differentiation of neuromesodermal progenitors and bone-producing osteogenic cells are controlled by RA. Changes to RA signaling activity have effects on the formation of the bones of the skull, the vertebrae and the development of teeth and regeneration of fin rays in fish. This review focuses on recent advances in these areas, with predominant emphasis on zebrafish, and highlights previously unknown roles for RA signaling in developmental processes.
Highlights
All-trans-retinoic acid (RA) is a small molecule that is critical during developmental processes of chordate embryos
Neuromesodermal progenitors (NMPs) play a central role during body axis elongation in vertebrates. They are a transient population of bipotential cells located in the caudal lateral epiblast (CLE), the node-streak border (NSB) and the chordoneural hinge (CNH) and are able to differentiate into mesodermal or neural tissue (Figure 1A) [68]
AGN193109, which stabilizes the heterodimeric complex of RA receptors (RAR/retinoid X receptors (RXRs)) with their transcriptional co-repressors, was applied to inhibit RA signaling during embryonic stem cells (ESC) differentiation, beginning at a differentiation stage that corresponds to cells from the CLE
Summary
All-trans-retinoic acid (RA) is a small molecule that is critical during developmental processes of chordate embryos. Neuromesodermal progenitors (NMPs) play a central role during body axis elongation in vertebrates They are a transient population of bipotential cells located in the caudal lateral epiblast (CLE), the node-streak border (NSB) and the chordoneural hinge (CNH) and are able to differentiate into mesodermal or neural tissue (Figure 1A) [68]. AGN193109, which stabilizes the heterodimeric complex of RA receptors (RAR/RXR) with their transcriptional co-repressors, was applied to inhibit RA signaling during ESC differentiation, beginning at a differentiation stage that corresponds to cells from the CLE This promoted the formation of the paraxial mesoderm, characterized by the upregulation of the gene markers Tbx and Msgn. 8 of sheath, a simultaneous contribution of chordoblasts from the inner side of the notochordal sheath has not been addressed to date [104]
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