Biology subjects

Bourgeois, S.

Publications and source records attributed to Bourgeois, S..

3 recordsLinked to original sources

bioRxiv2025

Nckx30c, a Drosophila K+-dependent Na+/Ca2+ exchanger, regulates temperature-sensitive convulsions and age-related neurodegeneration

Calcium (Ca2+) homeostasis is fundamental to neuronal physiology, including in the regulation of membrane excitability and synaptic transmission. Disruptions in the ion transporters regulating Ca2+ influx and efflux are clearly linked to seizure disorders and age-related neurodegenerative disease. Yet, the specific contributions of variants in genes encoding these transporters to neurological disease remain to be fully understood. Drosophila melanogaster has proven to be a powerful genetic model for uncovering such mechanisms, particularly through studies of mutants that display temperature-sensitive (TS) behavioral phenotypes. In a forward genetic screen, we identified a mutant line that exhibited TS convulsions along with progressive, age-dependent neurodegeneration. We mapped the mutation to Nckx30c, specifically within the transmembrane ion-binding region of this K+-dependent Na+/Ca2+ exchanger. Characterization of this mutant, together with a second Nckx30c allele, revealed TS convulsions, impaired locomotion, a markedly shortened lifespan, neurodegeneration with age, along with structural defects at larval and adult neuromuscular junctions (NMJs). Nckx30c mutants also displayed altered neural motor circuit performance. Gene expression analysis confirmed that Nckx30c levels were reduced in heads of Nckx30c loss-of-function mutants. Tissue-specific manipulation revealed that knockdown of Nckx30c in neurons recapitulated the TS convulsions, locomotor defects, and shortened lifespan phenotypes. Drosophila Nckx30c is highly conserved and shares homology with mammalian SLC24A2, a solute carrier family 24 member whose neurological role is not yet fully elucidated. Our work establishes Nckx30c as an essential regulator of neuronal health and provides an in vivo framework for investigating the contribution of SLC24A2 to neuronal Ca2+ homeostasis, seizures and age-related neurodegeneration.

neuroscience↗

bioRxiv2024

SNP panel for non-invasive genotyping of leopard (Panthera pardus)

Genetic resources for species monitoring should ideally be relevant for the species full distribution range, feasible economically and logistically, and validated for the range of sample types collected from the field. This is particularly important for large carnivores that are elusive and wide-ranging, where individual and population processes often traverse administrative borders, and where obtaining high-quality samples can be challenging. Here we present a small species-specific SNP panel for leopards. We used whole genome data from across the global range and RAD sequence data from Zambian leopards to select markers for assay development. These were ascertained for 590 individual leopards from eight African countries and final selection was based on marker variation and performance on non-invasive samples. The final 96 marker panel holds 5 mitochondrial markers for species recognition, 3 Y-markers for determination of individual sex, 3 X-markers and 85 somatic markers, with an associated genetic baseline holding nearly 900 individuals. The selected autosomal markers hold variation across the global range with high power to identify individuals (PID=2,45x10-35) and in most cases their provenance with high assignment probability (>95%). Markers were also selected based on their performance on samples with low target DNA content, with distinct genotype separation in the output marker plots. The genotypes from this panel are thus straightforward to analyze and do not require computationally challenging bioinformatic resources, making this a low cost and accessible resource for leopard monitoring and research.

genetics↗

bioRxiv2024

ER stress relief drives beta cell proliferation

Regenerating endogenous pancreatic {beta}-cells is a potentially curative yet currently elusive strategy for diabetes therapy. Mimicking the microenvironment of the developing pancreas and leveraging vascular signals that support pancreatic endocrinogenesis may promote {beta}-cell regeneration. We aimed to investigate whether recovery from experimental hypovascularization of the endocrine pancreas, achieved by modulating the transgenic production of a VEGF-A blocker in {beta}-cells, could trigger mouse {beta}-cell proliferation. Serendipitously, we found that transgene overexpression in {beta}-cells induces endoplasmic reticulum (ER) stress and that subsequent relief from this stress stimulates {beta}-cell proliferation independent of vessel recovery. Transient GFP overexpression in vivo and chemical induction of ER stress in vitro replicated this {beta}-cell cycling response. Our findings highlight the potential side effects of ER stress due to transgene overexpression in {beta}-cells and assert that ER stress relief serves as a potent regenerative stimulus.

molecular biology↗