Towards a Better Vision of Retinoic Acid Signaling during Eye Development
Open Access
- 19 January 2022
- Vol. 11 (3), 322
- https://doi.org/10.3390/cells11030322
Abstract
Retinoic acid (RA) functions as an essential signal for development of the vertebrate eye by controlling the transcriptional regulatory activity of RA receptors (RARs). During eye development, the optic vesicles and later the retina generate RA as a metabolite of vitamin A (retinol). Retinol is first converted to retinaldehyde by retinol dehydrogenase 10 (RDH10) and then to RA by all three retinaldehyde dehydrogenases (ALDH1A1, ALDH1A2, and ALDH1A3). In early mouse embryos, RA diffuses to tissues throughout the optic placode, optic vesicle, and adjacent mesenchyme to stimulate folding of the optic vesicle to form the optic cup. RA later generated by the retina is needed for further morphogenesis of the optic cup and surrounding perioptic mesenchyme; loss of RA at this stage leads to microphthalmia and cornea plus eyelid defects. RA functions by binding to nuclear RARs at RA response elements (RAREs) that either activate or repress transcription of key genes. Binding of RA to RARs regulates recruitment of transcriptional coregulators such as nuclear receptor coactivator (NCOA) or nuclear receptor corepressor (NCOR), which in turn control binding of the generic coactivator p300 or the generic corepressor PRC2. No genes have been identified as direct targets of RA signaling during eye development, so future studies need to focus on identifying such genes and their RAREs. Studies designed to learn how RA normally controls eye development in vivo will provide basic knowledge valuable for determining how developmental eye defects occur and for improving strategies to treat eye defects.Funding Information
- National Eye Institute (R01 EY031745)
This publication has 50 references indexed in Scilit:
- Transcriptomic Analysis of Murine Embryos Lacking Endogenous Retinoic Acid SignalingPLOS ONE, 2013
- Nuclear receptor coregulators: modulators of pathology and therapeutic targetsNature Reviews Endocrinology, 2012
- Topological domains in mammalian genomes identified by analysis of chromatin interactionsNature, 2012
- Genome-wide in Silico Identification of New Conserved and Functional Retinoic Acid Receptor Response Elements (Direct Repeats Separated by 5 bp)Online Journal of Public Health Informatics, 2011
- A unique chromatin signature uncovers early developmental enhancers in humansNature, 2010
- Retinoic acid signaling in perioptic mesenchyme represses Wnt signaling via induction of Pitx2 and Dkk2Developmental Biology, 2010
- The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye developmentDevelopmental Biology, 2008
- Gene expression profiling elucidates a specific role for RARγ in the retinoic acid-induced differentiation of F9 teratocarcinoma stem cellsBiochemical Pharmacology, 2008
- RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ developmentGenes & Development, 2007
- Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formationDevelopmental Dynamics, 2004