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http://hdl.handle.net/11375/22095
Title: | PRY-1/AXIN REGULATE AGING, LIPID METABOLISM AND SEAM-CELL ASYMMETRIC CELL DIVISION IN CAENORHABDITIS ELEGANS |
Other Titles: | AXIN SCAFFOLD: A SIGNALING MASTER AND METABOLIC RHEOSTAT |
Authors: | RANAWADE, AYUSH |
Advisor: | GUPTA, BHAGWATI |
Department: | Biology |
Keywords: | C. ELEGANS;WNT SIGNALING;LIPID METABOLISM;AGING |
Publication Date: | 2017 |
Abstract: | The nematode, Caenorhabditis elegans is an ideal animal model to study conserved mechanisms of developmental and postdevelopmental processes. Here, I describe the role of an Axin family member, pry-1, in aging, lipid metabolism, and seam cell development. Our analysis of pry-1 animals showed a catastrophic collapse of adult lifespan, which was accompanied with hallmarks of accelerated aging. Transcriptome profiling of pry-1 mutants revealed altered expression of genes associated with aging and lipid metabolism such as vitellogenins, fatty acid desaturases, lipases, fatty acid transporters and genes involved in cuticle synthesis. Consistent with this, pry-1 animals display significantly reduced levels of somatic lipids. Knockdowns of vitellogenins in the pry-1 background restored lifespan and lipid levels, suggesting that vitellogenins are necessary to mediate pry-1 function in aging and lipid metabolic processes. Additionally, lowered expression of desaturases and lipidomics analysis provided evidence of reduced fatty acid synthesis in pry-1 animals. In agreement with this, an exogenous supply of oleic acid restored depleted lipids in somatic tissues in addition to suppressing the short-lived phenotype of worms. In addition, transcriptome profiling for differentially expressed miRNAs in pry-1(mu38) identified heterochronic miRNAs (lin-4 and let-7 -family members) to act downstream of pry-1 /Axin. In C. elegans, these miRNAs are known to robustly regulate the stem-like, seam cell division. Loss of pry-1 function caused heterochronic defects such that the seam cells divide precociously to produce additional cells. The pry-1-miRNAs are involved in mediating silencing of the heterochronic gene, hbl-1, a C. elegans hunchback homolog, to regulate seam cell division. Furthermore, I report identification of novel miRNAs from C. elegans and C. briggsae. Overall, our findings demonstrate a novel role of the Wnt signaling regulator, pry-1/Axin, in the maintenance of adult lifespan that involves lipid homeostasis and regulation of heterochronic miRNA to control the developmental timing of seam cell division in C. elegans. |
URI: | http://hdl.handle.net/11375/22095 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Ayush-Ranawade-Thesis-2017.pdf | PHD THESIS | 46.24 MB | Adobe PDF | View/Open |
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