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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

CYP26B1 and zRalDH exhibit graded expression in higher auditory areas of adult zebra finch.The drawing in the top left indicates approximate regions shown in A–E; the drawings on the left depict brain areas shown on the right. The middle and right columns show sections processed for ISH for CYP26B1 and zRalDH. For all images, anterior is to the right and dorsal is up; medial to lateral is represented from top to bottom. CYP26B1 is expressed in a dorsoventral gradient-like pattern throughout the caudal, caudo-medial and caudo-lateral mesopallium (CM, CMM and CLM; arrows in middle panels point to region of high expression). This distribution does not overlap with zRalDH mRNA expression, which is absent in the mesopallium; some cells in the rostral part of the caudal nidopallium express zRalDH (arrows in right panels), tapering off caudally. For other abbreviations, see table 1. Scale bar  = 0.5 mm.
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pone-0111722-g015: CYP26B1 and zRalDH exhibit graded expression in higher auditory areas of adult zebra finch.The drawing in the top left indicates approximate regions shown in A–E; the drawings on the left depict brain areas shown on the right. The middle and right columns show sections processed for ISH for CYP26B1 and zRalDH. For all images, anterior is to the right and dorsal is up; medial to lateral is represented from top to bottom. CYP26B1 is expressed in a dorsoventral gradient-like pattern throughout the caudal, caudo-medial and caudo-lateral mesopallium (CM, CMM and CLM; arrows in middle panels point to region of high expression). This distribution does not overlap with zRalDH mRNA expression, which is absent in the mesopallium; some cells in the rostral part of the caudal nidopallium express zRalDH (arrows in right panels), tapering off caudally. For other abbreviations, see table 1. Scale bar  = 0.5 mm.

Mentions: We mapped the mRNA distribution of the retinoic acid degrading cytochromes CYP26A1, CYP26B1, and CYP26C1 in juvenile (6 males, PHD 20-68) and adult (7 males, 2 females) zebra finches. CYP26A1 and CYP26C1 distributions were low, broad and uniform, without evidence of regional enrichments (data not shown). In contrast, we successfully detected strong labeling at the known sites of CYP26A1 and CYP26C1 expression on sections of a zebra finch embryo (data not shown), demonstrating the effectiveness of the probes. CYP26B1 showed a complex pattern (fig. 14) that was partly adjacent to, but did not overlap with zRalDH expression. Within the telencephalon, CYP26B1 expression was restricted to the caudal mesopallium (CM), with highest expression in the dorsal-most part (fig. 14 and fig. 15) but some expression in the most fronto-lateral part (fig. 14.C), and a very small region in the hippocampus (fig. 14 and fig. S6.B–E). Outside of the telencephalon CYP26B1 was expressed in the medial habenula (fig. S6.F–H), the Purkinje cell layer of the cerebellum (fig. 14.A,B), and some scattered cells in the brain stem (fig. 14.B). Comparing distributions of the transcripts for the ATRA synthesizing zRalDH and the ATRA degrading CYP26B1 reveals differential expression combinations across the higher auditory regions (fig. 15): In CM (including both CMM and CLM), CYP26B1 expression varied along the dorso-ventral axis in a gradient-like manner, while zRalDH transcript was entirely absent. In NCM, which is devoid of CYP26B1 transcript, we noted some zRalDH expression in scattered cells concentrating in the most anterior part, while no zRalDH positive cells are found in the more posterior NCM (fig. 15.A–C). Note that this is in contrast to a previous study [25], where NCM did not show any zRalDH expression at all. CMM and NCM are separated by a thin layer of caudal nidopallium with high zRalDH expression, and field L2a which did not express either of the genes (fig. 15).


Long-distance retinoid signaling in the zebra finch brain.

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

CYP26B1 and zRalDH exhibit graded expression in higher auditory areas of adult zebra finch.The drawing in the top left indicates approximate regions shown in A–E; the drawings on the left depict brain areas shown on the right. The middle and right columns show sections processed for ISH for CYP26B1 and zRalDH. For all images, anterior is to the right and dorsal is up; medial to lateral is represented from top to bottom. CYP26B1 is expressed in a dorsoventral gradient-like pattern throughout the caudal, caudo-medial and caudo-lateral mesopallium (CM, CMM and CLM; arrows in middle panels point to region of high expression). This distribution does not overlap with zRalDH mRNA expression, which is absent in the mesopallium; some cells in the rostral part of the caudal nidopallium express zRalDH (arrows in right panels), tapering off caudally. For other abbreviations, see table 1. Scale bar  = 0.5 mm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230966&req=5

pone-0111722-g015: CYP26B1 and zRalDH exhibit graded expression in higher auditory areas of adult zebra finch.The drawing in the top left indicates approximate regions shown in A–E; the drawings on the left depict brain areas shown on the right. The middle and right columns show sections processed for ISH for CYP26B1 and zRalDH. For all images, anterior is to the right and dorsal is up; medial to lateral is represented from top to bottom. CYP26B1 is expressed in a dorsoventral gradient-like pattern throughout the caudal, caudo-medial and caudo-lateral mesopallium (CM, CMM and CLM; arrows in middle panels point to region of high expression). This distribution does not overlap with zRalDH mRNA expression, which is absent in the mesopallium; some cells in the rostral part of the caudal nidopallium express zRalDH (arrows in right panels), tapering off caudally. For other abbreviations, see table 1. Scale bar  = 0.5 mm.
Mentions: We mapped the mRNA distribution of the retinoic acid degrading cytochromes CYP26A1, CYP26B1, and CYP26C1 in juvenile (6 males, PHD 20-68) and adult (7 males, 2 females) zebra finches. CYP26A1 and CYP26C1 distributions were low, broad and uniform, without evidence of regional enrichments (data not shown). In contrast, we successfully detected strong labeling at the known sites of CYP26A1 and CYP26C1 expression on sections of a zebra finch embryo (data not shown), demonstrating the effectiveness of the probes. CYP26B1 showed a complex pattern (fig. 14) that was partly adjacent to, but did not overlap with zRalDH expression. Within the telencephalon, CYP26B1 expression was restricted to the caudal mesopallium (CM), with highest expression in the dorsal-most part (fig. 14 and fig. 15) but some expression in the most fronto-lateral part (fig. 14.C), and a very small region in the hippocampus (fig. 14 and fig. S6.B–E). Outside of the telencephalon CYP26B1 was expressed in the medial habenula (fig. S6.F–H), the Purkinje cell layer of the cerebellum (fig. 14.A,B), and some scattered cells in the brain stem (fig. 14.B). Comparing distributions of the transcripts for the ATRA synthesizing zRalDH and the ATRA degrading CYP26B1 reveals differential expression combinations across the higher auditory regions (fig. 15): In CM (including both CMM and CLM), CYP26B1 expression varied along the dorso-ventral axis in a gradient-like manner, while zRalDH transcript was entirely absent. In NCM, which is devoid of CYP26B1 transcript, we noted some zRalDH expression in scattered cells concentrating in the most anterior part, while no zRalDH positive cells are found in the more posterior NCM (fig. 15.A–C). Note that this is in contrast to a previous study [25], where NCM did not show any zRalDH expression at all. CMM and NCM are separated by a thin layer of caudal nidopallium with high zRalDH expression, and field L2a which did not express either of the genes (fig. 15).

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