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| Status |
Public on Jun 01, 2024 |
| Title |
Next Generation Sequencing and Quantitative Analysis of mRNAs in Caenorhabditis elegans Mutant Animals Exhibiting Impaired Hedgehog, mTORC2, or p38 Signaling |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
To maximize fitness, organisms must appropriately allocate energetic resources between essential cellular processes to maintain homeostasis. The nutritional regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern cellular metabolism is poorly understood. We identified a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis in C. elegans. We find that expression of two Hh ligands, GRD-3 and GRD-4, is controlled by the LIN-29/EGR transcription factor in the hypodermis, where the Hh secretion factor CHE-14/Dispatched also facilitates non-cell autonomous Hh signaling. Using C. elegans, we demonstrate that Hh metabolic regulation does not occur through the canonical Hh transcription factor, TRA-1/GLI, but rather through non-canonical signaling that engages mTOR Complex 2 (mTORC2) in the intestine. Hh mutants display impaired lipid homeostasis, including reduced lipoprotein synthesis and fat accumulation, decreased growth, and upregulation of autophagy factors, mimicking loss of mTORC2. Additionally, we found that Hh inhibits p38 MAPK signaling in parallel to mTORC2 activation and that both pathways act together to modulate of lipid homeostasis. Our findings show a non-canonical role for Hedgehog signaling in lipid metabolism via regulation of core homeostatic pathways and reveal a new mechanism by which developmental timing events govern metabolic decisions.
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| Overall design |
The mRNAs of wild-type and mutant day 1 adult animals were profiled by high-throughput sequencing, in triplicate.
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| Contributor(s) |
Dowen RH |
| Citation(s) |
39786994 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R35 GM137985 |
Regulation of lipid homeostasis by proliferative signaling pathways |
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL |
Robert Houston Dowen |
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| Submission date |
May 25, 2024 |
| Last update date |
Jan 10, 2025 |
| Contact name |
Robert Houston Dowen |
| E-mail(s) |
[email protected]
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| Organization name |
University of North Carolina at Chapel Hill
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| Department |
Cell Biology and Physiology
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| Lab |
133 N. Medical Drive
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| Street address |
321 Fordham Hall, CB7100
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| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7100 |
| Country |
USA |
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| Platforms (2) |
| GPL22765 |
Illumina HiSeq 4000 (Caenorhabditis elegans) |
| GPL26672 |
Illumina NovaSeq 6000 (Caenorhabditis elegans) |
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| Samples (36)
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| GSM8290226 |
MT333, SE, biol rep 1 |
| GSM8290227 |
MT333, SE, biol rep 2 |
| GSM8290228 |
MT333, SE, biol rep 3 |
| GSM8290229 |
DLS439, SE, biol rep 1 |
| GSM8290230 |
DLS439, SE, biol rep 2 |
| GSM8290231 |
DLS439, SE, biol rep 3 |
| GSM8290232 |
DLS440, SE, biol rep 1 |
| GSM8290233 |
DLS440, SE, biol rep 2 |
| GSM8290234 |
DLS440, SE, biol rep 3 |
| GSM8290235 |
DLS487, SE, biol rep 1 |
| GSM8290236 |
DLS487, SE, biol rep 2 |
| GSM8290237 |
DLS487, SE, biol rep 3 |
| GSM8290238 |
DLS490, SE, biol rep 1 |
| GSM8290239 |
DLS490, SE, biol rep 2 |
| GSM8290240 |
DLS490, SE, biol rep 3 |
| GSM8290241 |
MGH171, control RNAi, PE, biol rep 1 |
| GSM8290242 |
MGH171, control RNAi, PE, biol rep 2 |
| GSM8290243 |
MGH171, control RNAi, PE, biol rep 3 |
| GSM8290244 |
MGH171, tra-1 RNAi, PE, biol rep 1 |
| GSM8290245 |
MGH171, tra-1 RNAi, PE, biol rep 2 |
| GSM8290246 |
MGH171, tra-1 RNAi, PE, biol rep 3 |
| GSM8290247 |
N2, PE, biol rep 1 |
| GSM8290248 |
N2, PE, biol rep 2 |
| GSM8290249 |
N2, PE, biol rep 3 |
| GSM8290250 |
DLS938, PE, biol rep 1 |
| GSM8290251 |
DLS938, PE, biol rep 2 |
| GSM8290252 |
DLS938, PE, biol rep 3 |
| GSM8290253 |
DLS943, PE, biol rep 1 |
| GSM8290254 |
DLS943, PE, biol rep 2 |
| GSM8290255 |
DLS943, PE, biol rep 3 |
| GSM8290256 |
ZD101, PE, biol rep 1 |
| GSM8290257 |
ZD101, PE, biol rep 2 |
| GSM8290258 |
ZD101, PE, biol rep 3 |
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| Relations |
| BioProject |
PRJNA1116576 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE268363_DESeq2_DEGs_DLS439_v_DLS440_lin-29_study.txt.gz |
93.7 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS439_v_MT333_lin-29_study.txt.gz |
82.7 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS439_v_N2_lin-29_study.txt.gz |
328.1 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS440_v_MT333_lin-29_study.txt.gz |
59.5 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS440_v_N2_lin-29_study.txt.gz |
250.5 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS487_v_DLS490_Hh_study.txt.gz |
132.5 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS487_v_MT333_Hh_study.txt.gz |
259.7 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS487_v_N2_Hh_study.txt.gz |
88.7 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS490_v_MT333_Hh_study.txt.gz |
270.1 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS490_v_N2_Hh_study.txt.gz |
146.8 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS938_v_N2_tir-1_study.txt.gz |
330.3 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_DLS943_v_N2_tir-1_study.txt.gz |
132.3 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_MGH171_tra-1_v_MGH171_L4440_tra-1_study.txt.gz |
35.9 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_MT333_v_N2_Hh_study.txt.gz |
325.3 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_MT333_v_N2_lin-29_study.txt.gz |
321.8 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_DEGs_ZD101_v_N2_tir-1_study.txt.gz |
212.7 Kb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_norm_gene_counts_Hh_study.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_norm_gene_counts_lin-29_study.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_norm_gene_counts_tir-1_study.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE268363_DESeq2_norm_gene_counts_tra-1_study.txt.gz |
726.2 Kb |
(ftp)(http) |
TXT |
| GSE268363_FC_gene_read_counts_Hh_study.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| GSE268363_FC_gene_read_counts_lin-29_study.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| GSE268363_FC_gene_read_counts_tir-1_study.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| GSE268363_FC_gene_read_counts_tra-1_study.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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