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Updated: Feb 8, 2026

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Mouse but not zebrafish requires retinoic acid for control of neuromesodermal progenitors and body axis extension
Marie Berenguer1, Joseph J Lancman2, Thomas J Cunningham1
1Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Abstract:
In mouse, retinoic acid (RA) is required for the early phase of body axis extension controlled by a population of neuromesodermal progenitors (NMPs) in the trunk called expanding-NMPs, but not for the later phase of body axis extension controlled by a population of NMPs in the tail called depleting-NMPs. Recent observations suggest that zebrafish utilize depleting-NMPs but not expanding-NMPs for body axis extension. In zebrafish, a role for RA in body axis extension was not supported by previous studies on aldh1a2 (raldh2) mutants lacking RA synthesis. Here, by treating zebrafish embryos with an RA synthesis inhibitor, we also found that body axis extension and somitogenesis was not perturbed, although loss of pectoral fin and cardiac edema were observed consistent with previous studies. The conclusion that zebrafish diverges from mouse in not requiring RA for body axis extension is consistent with zebrafish lacking early expanding-NMPs to generate the trunk. We suggest that RA control of body axis extension was added to higher vertebrates during evolution of expanding-NMPs.
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