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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

RXRα expression in Area X, lMAN, and RA in relation to time of day and age.A: RXRα expression across the day. Bars represent the difference in normalized expression strength between a song nucleus and the surrounding area (“Δ RXRα inside nucleus-outside”, mean ± SEM); a 0 value indicates no expression difference, positive values indicate more expression inside than outside, negative values the opposite. At different times, expression compared to the surrounds varied significantly in lMAN, but not in Area X or RA; asterisk indicates significance by MANCOVA (Area X: F = 0.79, p = 0.471; lMAN: F = 5.7, p = 0.014; RA: F = 0.31, p = 0.736); for details, see Methods. During the day, the RXRα expression inside and outside lMAN was similar, whereas RXRα expression was lower in lMAN than in the surrounding nidopallium in the morning and evening. B: Representative bright field images of sagittal sections showing variation in RXRα expression in lMAN compared to surrounding nidopallium at different times of the day. C: RXRα expression across ages. Plotted is the same measure of expression strength as in A vs. age (post-hatch days), and linear fits; a significant decrease with age was seen in lMAN (MANCOVA, F = 4.72, p = 0.046) but not in Area X (F = 2.13, p = 0.165) or RA (F = 0.54, p = 0.476).
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pone-0111722-g013: RXRα expression in Area X, lMAN, and RA in relation to time of day and age.A: RXRα expression across the day. Bars represent the difference in normalized expression strength between a song nucleus and the surrounding area (“Δ RXRα inside nucleus-outside”, mean ± SEM); a 0 value indicates no expression difference, positive values indicate more expression inside than outside, negative values the opposite. At different times, expression compared to the surrounds varied significantly in lMAN, but not in Area X or RA; asterisk indicates significance by MANCOVA (Area X: F = 0.79, p = 0.471; lMAN: F = 5.7, p = 0.014; RA: F = 0.31, p = 0.736); for details, see Methods. During the day, the RXRα expression inside and outside lMAN was similar, whereas RXRα expression was lower in lMAN than in the surrounding nidopallium in the morning and evening. B: Representative bright field images of sagittal sections showing variation in RXRα expression in lMAN compared to surrounding nidopallium at different times of the day. C: RXRα expression across ages. Plotted is the same measure of expression strength as in A vs. age (post-hatch days), and linear fits; a significant decrease with age was seen in lMAN (MANCOVA, F = 4.72, p = 0.046) but not in Area X (F = 2.13, p = 0.165) or RA (F = 0.54, p = 0.476).

Mentions: Because of the known influence of retinoid signaling on circadian and seasonal rhythms in mammals [49] we explored whether RXRα expression in the song system varied with time of day, as well as age. Birds of different ages were sampled at different times of the day (without sampling at all times of the day for each age) and statistical significance for effects of age and time of the day were determined using MANCOVA (for details, see Materials & Methods). Compared to the adjacent tissue, RXRα mRNA expression varied with both age and time of the day in lMAN, but not in HVC, RA, or Area X (fig. 13). During the day (i.e. from 2 h after lights turned on until 2 h before lights turn off in a 12 12 h light cycle), RXRα expression was comparable between lMAN and surrounds (n = 14), whereas in the morning (within 20min after the lights turned on, before any singing took place; n = 3) and in the evening (within the last 1.5 h before the lights turned off, n = 2), RXRα expression was lower in lMAN than in the surrounding nidopallium (fig. 13.A,B). In adults, lMAN expressed less RXRα than the surrounding nidopallium. This difference was significantly less pronounced in juveniles (fig. 13.C).


Long-distance retinoid signaling in the zebra finch brain.

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

RXRα expression in Area X, lMAN, and RA in relation to time of day and age.A: RXRα expression across the day. Bars represent the difference in normalized expression strength between a song nucleus and the surrounding area (“Δ RXRα inside nucleus-outside”, mean ± SEM); a 0 value indicates no expression difference, positive values indicate more expression inside than outside, negative values the opposite. At different times, expression compared to the surrounds varied significantly in lMAN, but not in Area X or RA; asterisk indicates significance by MANCOVA (Area X: F = 0.79, p = 0.471; lMAN: F = 5.7, p = 0.014; RA: F = 0.31, p = 0.736); for details, see Methods. During the day, the RXRα expression inside and outside lMAN was similar, whereas RXRα expression was lower in lMAN than in the surrounding nidopallium in the morning and evening. B: Representative bright field images of sagittal sections showing variation in RXRα expression in lMAN compared to surrounding nidopallium at different times of the day. C: RXRα expression across ages. Plotted is the same measure of expression strength as in A vs. age (post-hatch days), and linear fits; a significant decrease with age was seen in lMAN (MANCOVA, F = 4.72, p = 0.046) but not in Area X (F = 2.13, p = 0.165) or RA (F = 0.54, p = 0.476).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111722-g013: RXRα expression in Area X, lMAN, and RA in relation to time of day and age.A: RXRα expression across the day. Bars represent the difference in normalized expression strength between a song nucleus and the surrounding area (“Δ RXRα inside nucleus-outside”, mean ± SEM); a 0 value indicates no expression difference, positive values indicate more expression inside than outside, negative values the opposite. At different times, expression compared to the surrounds varied significantly in lMAN, but not in Area X or RA; asterisk indicates significance by MANCOVA (Area X: F = 0.79, p = 0.471; lMAN: F = 5.7, p = 0.014; RA: F = 0.31, p = 0.736); for details, see Methods. During the day, the RXRα expression inside and outside lMAN was similar, whereas RXRα expression was lower in lMAN than in the surrounding nidopallium in the morning and evening. B: Representative bright field images of sagittal sections showing variation in RXRα expression in lMAN compared to surrounding nidopallium at different times of the day. C: RXRα expression across ages. Plotted is the same measure of expression strength as in A vs. age (post-hatch days), and linear fits; a significant decrease with age was seen in lMAN (MANCOVA, F = 4.72, p = 0.046) but not in Area X (F = 2.13, p = 0.165) or RA (F = 0.54, p = 0.476).
Mentions: Because of the known influence of retinoid signaling on circadian and seasonal rhythms in mammals [49] we explored whether RXRα expression in the song system varied with time of day, as well as age. Birds of different ages were sampled at different times of the day (without sampling at all times of the day for each age) and statistical significance for effects of age and time of the day were determined using MANCOVA (for details, see Materials & Methods). Compared to the adjacent tissue, RXRα mRNA expression varied with both age and time of the day in lMAN, but not in HVC, RA, or Area X (fig. 13). During the day (i.e. from 2 h after lights turned on until 2 h before lights turn off in a 12 12 h light cycle), RXRα expression was comparable between lMAN and surrounds (n = 14), whereas in the morning (within 20min after the lights turned on, before any singing took place; n = 3) and in the evening (within the last 1.5 h before the lights turned off, n = 2), RXRα expression was lower in lMAN than in the surrounding nidopallium (fig. 13.A,B). In adults, lMAN expressed less RXRα than the surrounding nidopallium. This difference was significantly less pronounced in juveniles (fig. 13.C).

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