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Neurogenesis in Response to Synthetic Retinoids at Different Temporal Scales

Haffez, H.; Khatib, T.; McCaffery, P.; Przyborski, S.; Redfern, C.; Whiting, A.

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H. Haffez

T. Khatib

P. McCaffery

C. Redfern


All-trans retinoic acid (ATRA) plays key roles in neurogenesis mediated by retinoic acid receptors (RARs). RARs are important targets for the therapeutic regulation of neurogenesis but effective drug development depends on modelling-based strategies to design high-specificity ligands in combination with good biological assays to discriminate between target-specificity and off-target effects. Using neuronal differentiation as a model, the aim of this study was to test the hypothesis that responses across different temporal scales and assay platforms can be used as comparable measures of retinoid activity. In biological assays based on cell phenotype or behaviour, two structurally similar synthetic retinoids, differing in RAR affinity and specificity, retained their relative activities across different temporal scales. In contrast, assays based on the transcriptional activation of specific genes in their normal genomic context were less concordant with biological assays. Gene-induction assays for retinoid activity as modulators of neurogenesis require careful interpretation in the light of variation in ligand-receptor affinity, receptor expression and gene function. A better characterization of neuronal phenotypes and their regulation by retinoids is badly needed as a framework for understanding how to regulate neuronal development.


Haffez, H., Khatib, T., McCaffery, P., Przyborski, S., Redfern, C., & Whiting, A. (2018). Neurogenesis in Response to Synthetic Retinoids at Different Temporal Scales. Molecular Neurobiology, 55(3), 1942-1950.

Journal Article Type Article
Acceptance Date Feb 3, 2017
Online Publication Date Feb 27, 2017
Publication Date Mar 1, 2018
Deposit Date Feb 27, 2017
Publicly Available Date Feb 28, 2017
Journal Molecular Neurobiology
Print ISSN 0893-7648
Electronic ISSN 1559-1182
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 55
Issue 3
Pages 1942-1950


Published Journal Article (Advance online version) (4 Mb)

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Copyright Statement
Advance online version © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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