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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

Overlapping expression of RARs and RXRs differ across song control nuclei, as well as between most song nuclei and their surroundings.Expression strength of all receptors based on visual estimates are schematically represented by symbol size (for RARs, data are from Jeong et al. (2005)). For all song nuclei except HVC, the receptor expression profile differs from the surroundings. Thus, each song nucleus has a unique combination of RAR(s)/RXR(s), which may lead to nucleus-specific sets of ATRA effects.
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pone-0111722-g016: Overlapping expression of RARs and RXRs differ across song control nuclei, as well as between most song nuclei and their surroundings.Expression strength of all receptors based on visual estimates are schematically represented by symbol size (for RARs, data are from Jeong et al. (2005)). For all song nuclei except HVC, the receptor expression profile differs from the surroundings. Thus, each song nucleus has a unique combination of RAR(s)/RXR(s), which may lead to nucleus-specific sets of ATRA effects.

Mentions: Expression of at least one RXR and one RAR overlapped in each one of the telencephalic song nuclei, qualifying them as potential targets of retinoid controlled gene transcription. The two groups of retinoid-related receptors, RXRs and RARs, are thought to mediate ATRA induced target gene transcription upon heterodimerization only [30]–[34]. But note that RXRs also hetero-dimerize with a multitude of other nuclear receptors, transcription factors and other peptides (reviewed by Lefebvre [51]). Thus, RXR mRNA distribution reflects a high functional diversity, and RXRs present in any region may serve other functions than ATRA-mediated signaling, irrespective of local ATRA presence. We did not investigate cellular colocalization of RXRs, RARs, and zRalDH. Except for RXRγ, however, receptors were expressed in most cells within the respective song nuclei, so that their expression is likely to overlap. We observed that: (1) All song nuclei but HVC exhibit RAR/RXR receptor expression profiles that differ from the surrounding tissue, and. (2) Each song nucleus has its own receptor expression profile (fig. 16). The three pallial song nuclei HVC, lMAN, and RA predominantly express RARα and RXRα, with lower levels in lMAN. HVC expresses RARγ [29]. RA has stronger RXRα expression than HVC and lMAN. The striatal Area X differs from the pallial nuclei most notably in that it expresses very little RXRα, but it also expresses RXRγ in a sparsely distributed population of large cells (fig. 6.B,C). They might correspond to the tonically-active fast-spiking pallidal cells in Area X, which provide input to the avian versions of the direct and indirect mammalian basal ganglia pathways [52], [53].


Long-distance retinoid signaling in the zebra finch brain.

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

Overlapping expression of RARs and RXRs differ across song control nuclei, as well as between most song nuclei and their surroundings.Expression strength of all receptors based on visual estimates are schematically represented by symbol size (for RARs, data are from Jeong et al. (2005)). For all song nuclei except HVC, the receptor expression profile differs from the surroundings. Thus, each song nucleus has a unique combination of RAR(s)/RXR(s), which may lead to nucleus-specific sets of ATRA effects.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111722-g016: Overlapping expression of RARs and RXRs differ across song control nuclei, as well as between most song nuclei and their surroundings.Expression strength of all receptors based on visual estimates are schematically represented by symbol size (for RARs, data are from Jeong et al. (2005)). For all song nuclei except HVC, the receptor expression profile differs from the surroundings. Thus, each song nucleus has a unique combination of RAR(s)/RXR(s), which may lead to nucleus-specific sets of ATRA effects.
Mentions: Expression of at least one RXR and one RAR overlapped in each one of the telencephalic song nuclei, qualifying them as potential targets of retinoid controlled gene transcription. The two groups of retinoid-related receptors, RXRs and RARs, are thought to mediate ATRA induced target gene transcription upon heterodimerization only [30]–[34]. But note that RXRs also hetero-dimerize with a multitude of other nuclear receptors, transcription factors and other peptides (reviewed by Lefebvre [51]). Thus, RXR mRNA distribution reflects a high functional diversity, and RXRs present in any region may serve other functions than ATRA-mediated signaling, irrespective of local ATRA presence. We did not investigate cellular colocalization of RXRs, RARs, and zRalDH. Except for RXRγ, however, receptors were expressed in most cells within the respective song nuclei, so that their expression is likely to overlap. We observed that: (1) All song nuclei but HVC exhibit RAR/RXR receptor expression profiles that differ from the surrounding tissue, and. (2) Each song nucleus has its own receptor expression profile (fig. 16). The three pallial song nuclei HVC, lMAN, and RA predominantly express RARα and RXRα, with lower levels in lMAN. HVC expresses RARγ [29]. RA has stronger RXRα expression than HVC and lMAN. The striatal Area X differs from the pallial nuclei most notably in that it expresses very little RXRα, but it also expresses RXRγ in a sparsely distributed population of large cells (fig. 6.B,C). They might correspond to the tonically-active fast-spiking pallidal cells in Area X, which provide input to the avian versions of the direct and indirect mammalian basal ganglia pathways [52], [53].

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