Biology subjects

Garrido-Maraver, J.

Publications and source records attributed to Garrido-Maraver, J..

2 recordsLinked to original sources

bioRxiv2024

ETS TRANSCRIPTION FACTOR POINTED CONTROLS GERMLINE SURVIVAL IN DROSOPHILA

AO_SCPLOWBSTRACTC_SCPLOWProper gonad development is a pre-requisite for gametogenesis and reproduction. During female gonad formation in Drosophila, the EGF receptor (EGFR) signalling pathway ensures the correct number of primordial germ cells (PGCs) populate the larval gonad. We study the gene pointed (pnt), which acts downstream of the EGFR receptor and belongs to the ETS transcription factor family, with a previously unknown function in gonadogenesis. We report that pnt is expressed in female larval gonads and later in the adult ovarian germline niche and that it is required to sustain proper gametogenesis. Loss of pnt function in female larval gonads, similar to the EGFR, induced PGC overproliferation. Conversely, we isolated a novel loss-of-function allele, pntaga, which resulted in agametic gonads and ovaries. While pntaga embryos developed gonads containing a normal complement of PGCs, these are subsequently lost by apoptosis during late larval and pupal stages. Molecular characterization of pntaga revealed reduced expression levels of the different pnt isoforms, unveiling a complex autoregulatory network involving the three Pnt proteins. We propose that germ line survival in Drosophila gonads requires a precise tuning of EGFR signalling to ensure the appropriate transcriptional activation of its target pnt.

developmental biology↗

bioRxiv2019

Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimers disease

Eukaryotic cells are complex systems containing internal compartments with specialised functions. Among these compartments, the endoplasmic reticulum (ER) plays a major role in processing proteins for modification and delivery to other organelles, whereas mitochondria generate energy in the form of ATP. Mitochondria and the ER form physical interactions, defined as mitochondria-ER contact sites (MERCS) to exchange metabolites such as calcium ions (Ca2+) and lipids. Sites of contact between mitochondria and the ER can regulate biological processes such as ATP generation and mitochondrial division. The interactions between mitochondria and the ER are dynamic and respond to the metabolic state of cells. Changes in MERCS have been linked to metabolic pathologies such as diabetes, neurodegenerative diseases and sleep disruption.\n\nHere we explored the consequences of increasing contacts between mitochondria and the ER in flies using a synthetic linker. We showed that enhancing MERCS increases locomotion and extends lifespan. We also showed that, in a Drosophila model of Alzheimers disease linked to toxic amyloid beta (A{beta}), linker expression can suppress motor impairment and extend lifespan. We conclude that strategies for increasing contacts between mitochondria and the ER may ameliorate symptoms of diseases associated with mitochondria dysfunction.

neuroscience↗