Summary of project PR001967
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001967. The data can be accessed directly via it's Project DOI: 10.21228/M8G72D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001967 |
| Project DOI: | doi: 10.21228/M8G72D |
| Project Title: | Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells |
| Project Type: | Untargeted Metabolomics and Lipidomics |
| Project Summary: | Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss of ifc causes massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthase schlank in glia of ifc mutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting that ifc function in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels. |
| Institute: | Washington University in St. Louis |
| Department: | Genetics, Medicine, Chemistry |
| Laboratory: | Skeath and Patti Laboratories |
| Last Name: | Cho |
| First Name: | Kevin |
| Address: | 1 Brookings Drive, Campus Box 1134, St. Louis, MO, 63130, USA |
| Email: | kevin.cho@wustl.edu |
| Phone: | 314-935-8813 |
Summary of all studies in project PR001967
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003162 | Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells | Drosophila melanogaster | Washington University in St. Louis | MS | 2024-04-12 | 1 | 40 | Uploaded data (748.9M)* |
