Neurogenesis in Response to Synthetic Retinoids at Different Temporal Scales

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

doi:10.1007/s12035-017-0440-7

Neurogenesis in Response to Synthetic Retinoids at Different Temporal Scales

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

Authors

H. Haffez

T. Khatib

P. McCaffery

Professor Stefan Przyborski stefan.przyborski@durham.ac.uk
Executive Dean

C. Redfern

Professor Andrew Whiting andy.whiting@durham.ac.uk
Emeritus Professor

Abstract

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.

Citation

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. https://doi.org/10.1007/s12035-017-0440-7

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
DOI	https://doi.org/10.1007/s12035-017-0440-7

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