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

In the absence of axonal input from HVC, ATRA induced reporter staining is reduced in RA of adult male zebra finches.Experimental design and time course are indicated by diagrams on the left and on top of photomicrographs. After surgical procedure, birds were allowed to survive for 14 days before reporter assay was performed. A–D: High power views of reporter expression induced in the monolayer by RA; dashed circles indicate position of RA. A and C: control hemispheres with intact HVC-to-RA projections. B and D: experimental hemispheres with HVC lesion (B) or knife-cut fibers (D).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111722-g012: In the absence of axonal input from HVC, ATRA induced reporter staining is reduced in RA of adult male zebra finches.Experimental design and time course are indicated by diagrams on the left and on top of photomicrographs. After surgical procedure, birds were allowed to survive for 14 days before reporter assay was performed. A–D: High power views of reporter expression induced in the monolayer by RA; dashed circles indicate position of RA. A and C: control hemispheres with intact HVC-to-RA projections. B and D: experimental hemispheres with HVC lesion (B) or knife-cut fibers (D).

Mentions: To determine whether terminal fibers from HVC projection neurons might be the source of the ATRA that induced LacZ expression in RA, we performed unilateral lesion ablations of HVC in 7 male zebra finches (3 adults and 2 juveniles) 14 days before subjecting their brain tissue to the ATRA reporter cell assay. In the absence of axonal input from HVC, ATRA-induced LacZ was strongly reduced or undetectable in RA (fig. 12.A,C). A similar result was obtained in 2 additional adult males where, instead of removing HVC, the fiber tracts from HVC to RA were cut with a scalpel 14 days before sacrifice (fig. 12.B,D). This procedure may have also affected fibers from lMAN to RA, as these travel in parallel to the HVCRA fibers. Even though the reporter assay used only allows a qualitative assessment of labeling intensity, it can be inferred from the very weak LacZ staining (specifically, very few to no cells in the reporter monolayer retained staining) that ATRA in RA after HVC removal or fiber cut was low to non-detectable. These findings, together with the diffuse zRalDH immunoreactivity seen in RA, suggest that ATRA in RA stems from outside sources; while HVC seems to be a major source of zRalDH enzyme/ATRA in RA, we cannot discard the possibility from these current experiments that LMAN is also a source.


Long-distance retinoid signaling in the zebra finch brain.

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

In the absence of axonal input from HVC, ATRA induced reporter staining is reduced in RA of adult male zebra finches.Experimental design and time course are indicated by diagrams on the left and on top of photomicrographs. After surgical procedure, birds were allowed to survive for 14 days before reporter assay was performed. A–D: High power views of reporter expression induced in the monolayer by RA; dashed circles indicate position of RA. A and C: control hemispheres with intact HVC-to-RA projections. B and D: experimental hemispheres with HVC lesion (B) or knife-cut fibers (D).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111722-g012: In the absence of axonal input from HVC, ATRA induced reporter staining is reduced in RA of adult male zebra finches.Experimental design and time course are indicated by diagrams on the left and on top of photomicrographs. After surgical procedure, birds were allowed to survive for 14 days before reporter assay was performed. A–D: High power views of reporter expression induced in the monolayer by RA; dashed circles indicate position of RA. A and C: control hemispheres with intact HVC-to-RA projections. B and D: experimental hemispheres with HVC lesion (B) or knife-cut fibers (D).
Mentions: To determine whether terminal fibers from HVC projection neurons might be the source of the ATRA that induced LacZ expression in RA, we performed unilateral lesion ablations of HVC in 7 male zebra finches (3 adults and 2 juveniles) 14 days before subjecting their brain tissue to the ATRA reporter cell assay. In the absence of axonal input from HVC, ATRA-induced LacZ was strongly reduced or undetectable in RA (fig. 12.A,C). A similar result was obtained in 2 additional adult males where, instead of removing HVC, the fiber tracts from HVC to RA were cut with a scalpel 14 days before sacrifice (fig. 12.B,D). This procedure may have also affected fibers from lMAN to RA, as these travel in parallel to the HVCRA fibers. Even though the reporter assay used only allows a qualitative assessment of labeling intensity, it can be inferred from the very weak LacZ staining (specifically, very few to no cells in the reporter monolayer retained staining) that ATRA in RA after HVC removal or fiber cut was low to non-detectable. These findings, together with the diffuse zRalDH immunoreactivity seen in RA, suggest that ATRA in RA stems from outside sources; while HVC seems to be a major source of zRalDH enzyme/ATRA in RA, we cannot discard the possibility from these current experiments that LMAN is also a source.

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