Skip to main content

Research Repository

Advanced Search

Application of Synthetic Photostable Retinoids Induces Novel Limb and Facial Phenotypes During Chick Embryogenesis In Vivo

Lopez-Real, R.E.; Budge, J.J.R.; Marder, T.B.; Whiting, A.; Hunt, P.N; Przyborski, S.A.

Application of Synthetic Photostable Retinoids Induces Novel Limb and Facial Phenotypes During Chick Embryogenesis In Vivo Thumbnail


Authors

R.E. Lopez-Real

J.J.R. Budge

T.B. Marder

P.N Hunt



Abstract

We have recently developed a range of synthetic retinoid analogues which include the compounds EC23 and EC19. They are stable on exposure to light and are predicted to be resistant to the normal metabolic processes involved in the inactivation of retinoids in vivo. Based on the position of the terminal carboxylic acid groups in the compounds we suggest that EC23 is a structural analogue of all-trans retinoic acid (ATRA), and EC19 is an analogue of 13-cis retinoic acid. Their effects on the differentiation of pluripotent stem cells has been previously described in vitro and are consistent with this hypothesis. We present herein the first description of the effects of these molecules in vivo. Retinoids were applied to the anterior limb buds of chicken embryos in ovo via ion-exchange beads. We found that retinoid EC23 produces effects on the wing digits similar to ATRA, but does so at two orders of magnitude lower concentration. When larger quantities of EC23 are applied, a novel phenotype is obtained involving production of multiple digit 1s on the anterior limb. This corresponds to differential effects of ATRA and EC23 on sonic hedgehog (shh) expression in the developing limb bud. With EC23 application we also find digit 1 phenotypes similar to thumb duplications described in the clinical literature. EC23 and ATRA are shown to have effects on the entire proximal–distal axis of the limb, including hitherto undescribed effects on the scapula. This includes suppression of expression of the scapula marker Pax1. EC23 also produces effects similar to those of ATRA on the developing face, producing reductions of the upper beak at concentrations two orders of magnitude lower than ATRA. In contrast, EC19, which is structurally very similar to EC23, has novel, less severe effects on the face and rarely alters limb development. EC19 and ATRA are effective at similar concentrations. These results further demonstrate the ability of retinoids to influence embryonic development. Moreover, EC23 represents a useful new tool to investigate developmental processes and probe the mechanisms underlying congenital abnormalities in vertebrates including man.

Citation

Lopez-Real, R., Budge, J., Marder, T., Whiting, A., Hunt, P., & Przyborski, S. (2014). Application of Synthetic Photostable Retinoids Induces Novel Limb and Facial Phenotypes During Chick Embryogenesis In Vivo. Journal of Anatomy, 224(4), 392-411. https://doi.org/10.1111/joa.12147

Journal Article Type Article
Publication Date Apr 1, 2014
Deposit Date Mar 21, 2013
Publicly Available Date Mar 28, 2024
Journal Journal of Anatomy
Print ISSN 0021-8782
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 224
Issue 4
Pages 392-411
DOI https://doi.org/10.1111/joa.12147
Keywords Chick, Craniofacial, Development, Limb, Pax1, Retinoic acid, Scapula, Sonic hedgehog, Synthetic retinoid.

Files

Published Journal Article (Advance online version) (2.1 Mb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Advance online version © 2013 The Authors Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.






You might also like



Downloadable Citations