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| Status |
Public on Sep 12, 2019 |
| Title |
Repression of an activity-dependent autocrine insulin signal is required for sensory neuron development in C. elegans |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The nervous system comprises diverse and highly specialized neuron-types, each expressing a unique set of genes that defines its functional properties. What molecular mechanisms generate diverse neuron types remains a central question in neuroscience. Our study of C. elegans chemosensory BAG neurons showed that a p38 MAP kinase (MAPK), PMK-3, is required for their proper differentiation and function (Brandt, J. and Ringstad, N. 2015). How p38 MAPKs function in neurodifferentiation is poorly understood. To better understand how pmk-3 promotes the BAG cell fate, we purified wild-type and pmk-3 mutant chemosensory BAG neurons and determined their transcriptomes using RNA-Seq. Expression of a number of genes that encode neuropeptides, including insulin-like peptides (ILPs), were up-regulated in pmk-3 mutant BAG neurons. Through analysis of mutations that restore expression of a BAG-fate marker to pmk-3 mutants, we additionally found that genes required for the release of neuropeptides, including UNC-31/CAPS, suppress pmk-3 mutant gene expression defects. These two observations suggested that the differentiation defects of pmk-3 mutants are associated with dysregulated release of peptide hormones. Indeed, we find that increased synthesis and release of ILPs from BAG during development causes a significant fraction of the gene expression and functional defects of pmk-3 mutant neurons. Together our data delineate a mechanism through which p38 MAPKs promote proper sensory neuron differentiation by inhibiting an autocrine insulin signal that represses expression of a BAG neuron fate. These findings reveal an unexpected role for insulin signaling in nervous system development and suggest that insulin-like factors are at the nexus of intrinsic genetic programs and extrinsic signaling mechanisms that regulate cell fate and neuronal differentiation.
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| Overall design |
Two biological replicates were analyzed for each of the 3 cell populations
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| Contributor(s) |
Horowitz LB, Ringstad N, Dolgalev I |
| Citation(s) |
31628111 |
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| Submission date |
Sep 11, 2019 |
| Last update date |
Dec 12, 2019 |
| Contact name |
Lauren Bayer Horowitz |
| E-mail(s) |
lauren.bayerhorowitz@nyumc.org
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| Phone |
2122630830
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| Organization name |
NYU School of Medicine
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| Department |
Cell Biology
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| Lab |
Ringstad
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| Street address |
540 1st Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL18245 |
Illumina HiSeq 2500 (Caenorhabditis elegans) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA564979 |
| SRA |
SRP221359 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE137267_Normalized_Average_Read_Count_Matrix.xlsx |
2.9 Mb |
(ftp)(http) |
XLSX |
| GSE137267_RAW.tar |
68.6 Mb |
(http)(custom) |
TAR (of TDF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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