Limits...
Long-distance retinoid signaling in the zebra finch brain.

Roeske TC, Scharff C, Olson CR, Nshdejan A, Mello CV - PLoS ONE (2014)

Bottom Line: Our results show that (1) ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts.This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2) Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN), receptor expression is dynamically regulated in a circadian and age-dependent manner. (3) High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling.Together, our survey across multiple connected song nuclei and auditory brain regions underscores the prominent role of retinoid signaling in modulating the circuitry that underlies the acquisition and production of learned vocalizations.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Hunter College, City University of New York, New York, New York, United States of America.

ABSTRACT
All-trans retinoic acid (ATRA), the main active metabolite of vitamin A, is a powerful signaling molecule that regulates large-scale morphogenetic processes during vertebrate embryonic development, but is also involved post-natally in regulating neural plasticity and cognition. In songbirds, it plays an important role in the maturation of learned song. The distribution of the ATRA-synthesizing enzyme, zRalDH, and of ATRA receptors (RARs) have been described, but information on the distribution of other components of the retinoid signaling pathway is still lacking. To address this gap, we have determined the expression patterns of two obligatory RAR co-receptors, the retinoid X receptors (RXR) α and γ, and of the three ATRA-degrading cytochromes CYP26A1, CYP26B1, and CYP26C1. We have also studied the distribution of zRalDH protein using immunohistochemistry, and generated a refined map of ATRA localization, using a modified reporter cell assay to examine entire brain sections. Our results show that (1) ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts. This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2) Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN), receptor expression is dynamically regulated in a circadian and age-dependent manner. (3) High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling. Together, our survey across multiple connected song nuclei and auditory brain regions underscores the prominent role of retinoid signaling in modulating the circuitry that underlies the acquisition and production of learned vocalizations.

No MeSH data available.


Related in: MedlinePlus

Induction of ATRA reporter expression by song nuclei that do not express zRalDH in adult male zebra finch.Line drawing on top indicates position of song nuclei. Left panels: detail views of zRalDH expression by ISH. Middle panels: Sites of ATRA presence by reporter cell assay. Right panels: summary and examples of transcript distribution for retinoid receptors. Data for RAR expression are from Jeong et al., 2005. Brain diagram on top indicates position of song control nuclei. In all panels, frontal is to the right and dorsal is up. A: Area X; B: RA. In both nuclei, zRalDH is not expressed, but ATRA-induced reporter expression is detected, as well as receptors that may mediate ATRA effects.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4230966&req=5

pone-0111722-g009: Induction of ATRA reporter expression by song nuclei that do not express zRalDH in adult male zebra finch.Line drawing on top indicates position of song nuclei. Left panels: detail views of zRalDH expression by ISH. Middle panels: Sites of ATRA presence by reporter cell assay. Right panels: summary and examples of transcript distribution for retinoid receptors. Data for RAR expression are from Jeong et al., 2005. Brain diagram on top indicates position of song control nuclei. In all panels, frontal is to the right and dorsal is up. A: Area X; B: RA. In both nuclei, zRalDH is not expressed, but ATRA-induced reporter expression is detected, as well as receptors that may mediate ATRA effects.

Mentions: We detected ATRA-induced LacZ expression in all brain areas that express zRalDH, including HVC and lMAN (fig. 8), confirming previous results [21]. Interestingly, ATRA also induced LacZ expression in some regions distant from zRalDH expression sites, such as Area X and RA (fig. 9). It seems unlikely that the RA and Area X signal was due to diffusion since there was less LacZ expression in the arcopallial tissue surrounding RA than inside the nucleus (fig. 9.B), which would not be the case if ATRA had diffused from around RA into the nucleus. Furthermore, the closest zRalDH mRNA expression sites, lMAN and its surrounding nidopallium, are too distant to account for the observed distribution of ATRA-induced gene expression (fig. 9).


Long-distance retinoid signaling in the zebra finch brain.

Roeske TC, Scharff C, Olson CR, Nshdejan A, Mello CV - PLoS ONE (2014)

Induction of ATRA reporter expression by song nuclei that do not express zRalDH in adult male zebra finch.Line drawing on top indicates position of song nuclei. Left panels: detail views of zRalDH expression by ISH. Middle panels: Sites of ATRA presence by reporter cell assay. Right panels: summary and examples of transcript distribution for retinoid receptors. Data for RAR expression are from Jeong et al., 2005. Brain diagram on top indicates position of song control nuclei. In all panels, frontal is to the right and dorsal is up. A: Area X; B: RA. In both nuclei, zRalDH is not expressed, but ATRA-induced reporter expression is detected, as well as receptors that may mediate ATRA effects.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230966&req=5

pone-0111722-g009: Induction of ATRA reporter expression by song nuclei that do not express zRalDH in adult male zebra finch.Line drawing on top indicates position of song nuclei. Left panels: detail views of zRalDH expression by ISH. Middle panels: Sites of ATRA presence by reporter cell assay. Right panels: summary and examples of transcript distribution for retinoid receptors. Data for RAR expression are from Jeong et al., 2005. Brain diagram on top indicates position of song control nuclei. In all panels, frontal is to the right and dorsal is up. A: Area X; B: RA. In both nuclei, zRalDH is not expressed, but ATRA-induced reporter expression is detected, as well as receptors that may mediate ATRA effects.
Mentions: We detected ATRA-induced LacZ expression in all brain areas that express zRalDH, including HVC and lMAN (fig. 8), confirming previous results [21]. Interestingly, ATRA also induced LacZ expression in some regions distant from zRalDH expression sites, such as Area X and RA (fig. 9). It seems unlikely that the RA and Area X signal was due to diffusion since there was less LacZ expression in the arcopallial tissue surrounding RA than inside the nucleus (fig. 9.B), which would not be the case if ATRA had diffused from around RA into the nucleus. Furthermore, the closest zRalDH mRNA expression sites, lMAN and its surrounding nidopallium, are too distant to account for the observed distribution of ATRA-induced gene expression (fig. 9).

Bottom Line: Our results show that (1) ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts.This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2) Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN), receptor expression is dynamically regulated in a circadian and age-dependent manner. (3) High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling.Together, our survey across multiple connected song nuclei and auditory brain regions underscores the prominent role of retinoid signaling in modulating the circuitry that underlies the acquisition and production of learned vocalizations.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Hunter College, City University of New York, New York, New York, United States of America.

ABSTRACT
All-trans retinoic acid (ATRA), the main active metabolite of vitamin A, is a powerful signaling molecule that regulates large-scale morphogenetic processes during vertebrate embryonic development, but is also involved post-natally in regulating neural plasticity and cognition. In songbirds, it plays an important role in the maturation of learned song. The distribution of the ATRA-synthesizing enzyme, zRalDH, and of ATRA receptors (RARs) have been described, but information on the distribution of other components of the retinoid signaling pathway is still lacking. To address this gap, we have determined the expression patterns of two obligatory RAR co-receptors, the retinoid X receptors (RXR) α and γ, and of the three ATRA-degrading cytochromes CYP26A1, CYP26B1, and CYP26C1. We have also studied the distribution of zRalDH protein using immunohistochemistry, and generated a refined map of ATRA localization, using a modified reporter cell assay to examine entire brain sections. Our results show that (1) ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts. This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2) Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN), receptor expression is dynamically regulated in a circadian and age-dependent manner. (3) High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling. Together, our survey across multiple connected song nuclei and auditory brain regions underscores the prominent role of retinoid signaling in modulating the circuitry that underlies the acquisition and production of learned vocalizations.

No MeSH data available.


Related in: MedlinePlus