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Ramesh, N. A.

Publications and source records attributed to Ramesh, N. A..

2 recordsLinked to original sources

Post-eclosion growth in the Drosophila Ejaculatory Duct is driven by Juvenile Hormone signaling and is essential for male fertility

The Drosophila Ejaculatory duct (ED) is a secretory tissue of the somatic male reproductive system. The ED is involved in the secretion of seminal fluid components and ED-specific antimicrobial peptides that aid in fertility and the female post-mating response. The ED is composed of secretory epithelial cells surrounded by a layer of innervated contractile muscle. The ED grows in young adult males during the first 24h post-eclosion, but the cell cycle status of the ED secretory cells and the role of post-eclosion ED growth have been unexplored. Here, we show that secretory cells of the adult Drosophila ED undergo variant cell cycles lacking mitosis called the endocycle, that lead to an increase in the cell and organ size of the ED post eclosion. The cells largely exit the endocycle by day 3 of adulthood, when the growth of the ED ceases, resulting in a tissue containing cells of ploidies ranging from 8C-32C. The size of the ED directly correlates with the ploidy of the secretory cells, with additional ectopic endocycles increasing organ size. When endoreplication is compromised in ED secretory cells, it leads to reduced organ size, reduced protein synthesis and compromised fertility. We provide evidence that the growth and endocycling in the young adult male ED is dependent on Juvenile hormone (JH) signaling and we suggest that hormone-induced early adult endocycling is required for optimal fertility and function of the ED tissue. We propose to use the ED as a post-mitotic tissue model to study the role of polyploidy in regulating secretory tissue growth and function.

developmental biology↗

A genetic and physiological model of renal dysfunction in Lowe syndrome

Lowe syndrome (LS) is an X-linked recessive genetic disorder characterized by renal dysfunction, neurodevelopmental defects, and cataract. The affected gene, OCRL encodes for a polyphosphoinositide 5-phosphatase. OCRL is localized to multiple sub-cellular locations in the endolysosomal system and defects in these organelles have been described in human cells depleted of OCRL. However, the relationship of the endolysosomal defects in OCRL depleted cells to the altered physiology of kidney cells of LS patients has not been completely determined. Here we model the kidney phenotypes of LS using a Drosophila nephrocyte model. Using this model system, we demonstrate that OCRL plays a cell-autonomous role in nephrocyte function. Deletion of the only OCRL ortholog in Drosophila (dOCRL) leads to cell-autonomous defects in larval nephrocyte structure and function. Null mutants of dOCRL (dOCRLKO) show defects in the endolysosomal system of larval nephrocytes that are associated with physiological defects in nephrocyte function. These defects could be rescued by reconstitution with a human OCRL transgene but not with a phosphatase dead version or a human LS patient derived mutation. Overall, this work provides a model system to understand the mechanisms by which the sub-cellular changes from loss of OCRL leads to defects in kidney function in human patients.

cell biology↗