Systematic Gene Expression Mapping Clusters Nuclear Receptors According to Their Function in the Brain

Gofflot, Françoise; Chartoire, Nathalie; Vasseur, Laurent; Heikkinen, Sami; Dembelé, Doulaye; Merrer, Julie Le; Auwerx, Johan

doi:10.1016/j.cell.2007.09.012

Cited by 142 publications

(133 citation statements)

References 49 publications

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…1A). The expression profiles generally correspond to the known distribution and sites of action of different receptors (9), and provide comprehensive information at the higher aggregation level of brain regions described here. For example, Esr1 is highly expressed in the HY, OLF, and cortical subpalate.…”

Section: Resultsmentioning

confidence: 79%

“…In situ hybridization (ISH) has been used to identify the functional roles of the 49 NR genes in adult mouse brain based on the clustering of the NR expression patterns in anatomical and regulatory networks (9). In this study, we substantially extended this approach to identify targets and signaling partners of the steroid receptors, and relationships between different regions of the mouse brain, based on genome-wide coexpression with steroid receptors.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions

Mahfouz

Lelieveldt

Grefhorst

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Steroid receptors are pleiotropic transcription factors that coordinate adaptation to different physiological states. An important target organ is the brain, but even though their effects are well studied in specific regions, brain-wide steroid receptor targets and mediators remain largely unknown due to the complexity of the brain. Here, we tested the idea that novel aspects of steroid action can be identified through spatial correlation of steroid receptors with genome-wide mRNA expression across different regions in the mouse brain. First, we observed significant coexpression of six nuclear receptors (NRs) [androgen receptor (Ar), estrogen receptor alpha (Esr1), estrogen receptor beta (Esr2), glucocorticoid receptor (Gr), mineralocorticoid receptor (Mr), and progesterone receptor (Pgr)] with sets of steroid target genes that were identified in single brain regions. These coexpression relationships were also present in distinct other brain regions, suggestive of as yet unidentified coordinate regulation of brain regions by, for example, glucocorticoids and estrogens. Second, coexpression of a set of 62 known NR coregulators and the six steroid receptors in 12 nonoverlapping mouse brain regions revealed selective downstream pathways, such as Pak6 as a mediator for the effects of Ar and Gr on dopaminergic transmission. Third, Magel2 and Irs4 were identified and validated as strongly responsive targets to the estrogen diethylstilbestrol in the mouse hypothalamus. The brain-and genome-wide correlations of mRNA expression levels of six steroid receptors that we provide constitute a rich resource for further predictions and understanding of brain modulation by steroid hormones. neuroendocrinology | nuclear receptors | transcription regulation | estrogens | glucocorticoids S teroid receptors are part of the superfamily of nuclear receptors (NRs) that act as transcription factors regulating expression of numerous biologically important target genes (1). Their transcriptional activity is induced by steroid hormones, which respond to changed demands in terms of reproductive status, mineral balance, or stressful physical and psychological challenges. A crucial site of action is the brain, where these hormones have strong modulatory effects on physiological regulation, cognitive function, mood, and behavior. They do so by changing cellular responsiveness to a variety of neurotransmitters and peptides, and by inducing morphological changes (2, 3).Understanding the effects of steroid hormones on the brain faces the challenge to identify in as many as 900 different brain nuclei (4) both the highly cell-specific target genes that mediate the hormone effects (5, 6) and the signaling factors that mediate or influence steroid receptor signaling. The latter include proteins affecting prereceptor metabolism, interacting transcription factors (7), and downstream NR coregulator proteins (1). Even if the effects of steroid hormones are well-studied in specific regions (1, 8), overall, the brain steroid receptor targets and mediators ...

show abstract

Section: Resultsmentioning

confidence: 79%

mentioning

confidence: 99%

Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions

Mahfouz

Lelieveldt

Grefhorst

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…There are three known PPAR isoforms, PPARα, PPARβ/δ, and PPARγ, which are located throughout most peripheral tissues, as well as in neurons and glia in the brain (Gofflot et al, 2007;Moreno, FarioliVecchioli, & Ceru, 2004;Sarruf et al, 2009;Woods et al, 2003). Activation of PPAR attenuates innate immune signaling, thereby mediating antiinflammatory and neuroprotective processes (Berger & Moller, 2002;Kapadia, Yi, & Vemuganti, 2008;Landreth & Heneka, 2001;Pistis & Melis, 2010).…”

Section: Ppar Agonistsmentioning

confidence: 99%

Opportunities for the Development of Neuroimmune Therapies in Addiction

Ray

Roche

Heinzerling

et al. 2014

International Review of Neurobiology

View full text Add to dashboard Cite

“…By virtue of the mouse genome project and other large scale cDNA sequencing approaches, computer software tools are available to mine for tissue-specific genes or ESTs from the constructed databases (1)(2)(3). Over 90% of the information for the entire mouse genome was elucidated by the mouse genome project consortium and is now available in databases, such as Mouse Genome Resources (http://www.ncbi.nlm.nih.gov /projects/genome/guide/mouse/) and Mouse Ensembl (http:// www.ensembl.org/Mus_musculus/) (4).…”

Section: Introductionmentioning

confidence: 99%

Characterization of tissue-specific mbu-3 gene expression in the mouse central nervous system

Lee

Cho²,

Kim

2008

BMB Reports

View full text Add to dashboard Cite

Mbu-3 is a novel mouse brain unigene that was identified by digital differential display. In this study, expression of the gene was chased through developmental stages and the protein product was identified in the brain. The cDNA sequence was 3,995-bp long and contained an ORF of 745 AA. Database searches revealed that the chicken SST273 gene containing LRR-and Ig-domain was an mbu-3 orthologue. Tissue specificity for the gene was examined in embryos and in brains at post-natal and adult stages. During the embryonic stages, mbu-3 was localized to the central nervous system in the brain and spinal cord. In the early post-natal stages, the gene was evenly expressed in the brain. However, with aging, expression was confined to specific regions, particularly the hippocampus.

show abstract

Systematic Gene Expression Mapping Clusters Nuclear Receptors According to Their Function in the Brain

Cited by 142 publications

References 49 publications

Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions

Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions

Opportunities for the Development of Neuroimmune Therapies in Addiction

Characterization of tissue-specific mbu-3 gene expression in the mouse central nervous system

Contact Info

Product

Resources

About