Dataset Information

Development of melanopsin-based irradiance detecting circuitry.

ABSTRACT:

Background

Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown.

Results

Here, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin innervating the SCN at postnatal ages, unlike most RGCs, which innervate their image-forming targets embryonically. Moreover, the appearance of ipRGC axons in the OPN coincides precisely with the onset of the pupillary light response.

Conclusions

Some ipRGCs differ not only functionally but also developmentally from RGCs that mediate pattern-forming vision.

SUBMITTER: McNeill DS

PROVIDER: S-EPMC3070623 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Publications

Development of melanopsin-based irradiance detecting circuitry.

McNeill David S DS Sheely Catherine J CJ Ecker Jennifer L JL Badea Tudor C TC Morhardt Duncan D Guido William W Hattar Samer S

Neural development 20110318

<h4>Background</h4>Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry de ...[more]

PMID: 21418557

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Project description:BACKGROUND:Genome-wide association studies have identified many susceptibility loci for obesity. However, missing heritability problem is still challenging and ignorance of genetic interactions is believed to be an important cause. Current methods for detecting interactions usually do not consider regulatory elements in non-coding regions. Interaction analyses within chromatin regulatory circuitry may identify new susceptibility loci. METHODS:We developed a pipeline named interaction analyses within chromatin regulatory circuitry (IACRC), to identify genetic interactions impacting body mass index (BMI). Potential interacting SNP pairs were obtained based on Hi-C datasets, PreSTIGE (Predicting Specific Tissue Interactions of Genes and Enhancers) algorithm, and super enhancer regions. SNP?×?SNP analyses were next performed in three GWAS datasets, including 2286 unrelated Caucasians from Kansas City, 3062 healthy Caucasians from the Gene Environment Association Studies initiative, and 3164 Hispanic subjects from the Women's Health Initiative. RESULTS:A total of 16,643,227 SNP?×?SNP analyses were performed. Meta-analyses showed that two SNP pairs, rs6808450-rs9813534 (combined P?=?2.39?×?10-9) and rs6808450-rs3773306 (combined P?=?2.89?×?10-9) were associated with BMI after multiple testing corrections. Single-SNP analyses did not detect significant association signals for these three SNPs. In obesity relevant cells, rs6808450 is located in intergenic enhancers, while rs9813534 and rs3773306 are located in the region of strong transcription regions of CAND2 and RPL32, respectively. The expression of CAND2 was significantly downregulated after the differentiation of human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cells (P?=?0.0241). Functional validation in the International Mouse Phenotyping Consortium database showed that CAND2 was associated with increased lean body mass and decreased total body fat amount. CONCLUSIONS:Detecting epistasis within chromatin regulatory circuitry identified CAND2 as a novel obesity susceptibility gene. We hope IACRC could facilitate the interaction analyses for complex diseases and offer new insights into solving the missing heritability problem.

Dataset Information

Development of melanopsin-based irradiance detecting circuitry.

Background

Results

Conclusions

Publications

Development of melanopsin-based irradiance detecting circuitry.

Similar Datasets

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