Transcriptomic Analysis of Murine Embryos Lacking Endogenous Retinoic Acid Signaling

29Citations
Citations of this article
76Readers
Mendeley users who have this article in their library.

Abstract

Retinoic acid (RA), an active derivative of the liposoluble vitamin A (retinol), acts as an important signaling molecule during embryonic development, regulating phenomenons as diverse as anterior-posterior axial patterning, forebrain and optic vesicle development, specification of hindbrain rhombomeres, pharyngeal arches and second heart field, somitogenesis, and differentiation of spinal cord neurons. This small molecule directly triggers gene activation by binding to nuclear receptors (RARs), switching them from potential repressors to transcriptional activators. The repertoire of RA-regulated genes in embryonic tissues is poorly characterized. We performed a comparative analysis of the transcriptomes of murine wild-type and Retinaldehyde Dehydrogenase 2 null-mutant (Raldh2-/-) embryos - unable to synthesize RA from maternally-derived retinol - using Affymetrix DNA microarrays. Transcriptomic changes were analyzed in two embryonic regions: anterior tissues including forebrain and optic vesicle, and posterior (trunk) tissues, at early stages preceding the appearance of overt phenotypic abnormalities. Several genes expected to be downregulated under RA deficiency appeared in the transcriptome data (e.g. Emx2, Foxg1 anteriorly, Cdx1, Hoxa1, Rarb posteriorly), whereas reverse-transcriptase-PCR and in situ hybridization performed for additional selected genes validated the changes identified through microarray analysis. Altogether, the affected genes belonged to numerous molecular pathways and cellular/organismal functions, demonstrating the pleiotropic nature of RA-dependent events. In both tissue samples, genes upregulated were more numerous than those downregulated, probably due to feedback regulatory loops. Bioinformatic analyses highlighted groups (clusters) of genes displaying similar behaviors in mutant tissues, and biological functions most significantly affected (e.g. mTOR, VEGF, ILK signaling in forebrain tissues; pyrimidine and purine metabolism, calcium signaling, one carbon metabolism in posterior tissues). Overall, these data give an overview of the gene expression changes resulting from embryonic RA deficiency, and provide new candidate genes and pathways that may help understanding retinoid-dependent molecular events. © 2013 Paschaki et al.

References Powered by Scopus

Open source clustering software

2503Citations
N/AReaders
Get full text

Embryonic retinoic acid synthesis is essential for early mouse post- implantation development

925Citations
N/AReaders
Get full text

Gene expression regulation by retinoic acid

855Citations
N/AReaders
Get full text

Cited by Powered by Scopus

An adverse outcome pathway framework for neural tube and axial defects mediated by modulation of retinoic acid homeostasis

58Citations
N/AReaders
Get full text

HMGCS2 is a key ketogenic enzyme potentially involved in type 1 diabetes with high cardiovascular risk

47Citations
N/AReaders
Get full text

Mechanisms of Feedback Regulation of Vitamin A Metabolism

35Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Paschaki, M., Schneider, C., Rhinn, M., Thibault-Carpentier, C., Dembélé, D., Niederreither, K., & Dollé, P. (2013). Transcriptomic Analysis of Murine Embryos Lacking Endogenous Retinoic Acid Signaling. PLoS ONE, 8(4). https://doi.org/10.1371/journal.pone.0062274

Readers over time

‘13‘14‘15‘16‘17‘18‘19‘20‘21‘22‘23‘24‘25036912

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 31

50%

Researcher 23

37%

Professor / Associate Prof. 8

13%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 34

56%

Biochemistry, Genetics and Molecular Bi... 21

34%

Medicine and Dentistry 4

7%

Neuroscience 2

3%

Save time finding and organizing research with Mendeley

Sign up for free
0