Biology subjects

Charpentier, C.

Publications and source records attributed to Charpentier, C..

4 recordsLinked to original sources

bioRxiv2026

CACNA2D4 variants are associated with exertional heat stroke susceptibility

Exertional Heat Stroke (EHS) is a life-threatening disease defined by severe hyperthermia and sudden neurological dysfunction in healthy individuals exposed to intense physical exercise. As is the case with some forms of malignant hyperthermia, mutations in genes involved in skeletal muscle contraction could predispose some patients to EHS. However, the genetic basis of EHS remains poorly documented. Here we identify EHS-associated variants in the CACNA2D4 gene encoding the Cav Ca2+ channel subunit, 2{delta}4, and describe their impact in heterologous expression systems and a knock-in mutant mouse strain heterozygous for the S299R variant (S299R+/-). In transfected cells, each CACNA2D4 variant, including S299R, affected the trafficking and function of 2{delta}4 and its regulation of the Cav1.1 channel. S299R+/-mice showed EHS-like crisis with signs of rhabdomyolysis and an elevation in core body temperature when submitted to an intense exercise protocol. We show that a CACNA2D4 transcript is expressed in mouse skeletal muscle and that the presence of the S299R variant in 2{delta}4 induces a modification in the calcium flux triggered by muscle cell depolarization. Altogether, our data reveal an unexpected connection between CACNA2D4 gene variants and pathophysiological alterations in skeletal muscle Ca2+ signaling that may increase EHS susceptibility.

genetics↗

bioRxiv2023

rphenoscate: An R package for semantic-aware evolutionary analyses of anatomical traits

O_LIOrganismal anatomy is a complex hierarchical system of interconnected anatomical entities often producing dependencies among multiple morphological characters. Ontologies provide a formalized and computable framework for representing and incorporating prior biological knowledge about anatomical dependencies in models of trait evolution. Further, ontologies offer new opportunities for assembling and working with semantic representations of morphological data. C_LIO_LIIn this work we present a new R package--rphenoscate--that enables incorporating ontological knowledge in evolutionary analyses and exploring semantic patterns of morphological data. In conjunction with rphenoscape it also allows for assembling synthetic phylogenetic character matrices from semantic phenotypes of morphological data. We showcase the new package functionalities with three data sets from bees and fishes. C_LIO_LIWe demonstrate that ontology knowledge can be employed to automatically set up ontologyinformed evolutionary models that account for trait dependencies in the context of stochastic character mapping. We also demonstrate how ontology annotations can be explored to interrogate patterns of morphological evolution. Finally, we demonstrate that synthetic character matrices assembled from semantic phenotypes retain most of the phylogenetic information of the original data set. C_LIO_LIOntologies will become an increasingly important tool not only for enabling prior anatomical knowledge to be integrated into phylogenetic methods but also to make morphological data FAIR compliant--a critical component of the ongoing phenomics revolution. Our new package offers key advancements toward this goal. C_LI

evolutionary biology↗

bioRxiv2020

Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical circuit assembly

Neuron-glia relationships play a critical role in the regulation of synapse formation and neuronal specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. Here we demonstrate that the canonical Sonic hedgehog (Shh) pathway is active in cortical astrocytes, where it acts to coordinate layer-specific synaptic connectivity and functional circuit development. We show that Ptch1 is a Shh receptor that is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of layer-specific astrocyte genes involved in regulating synapse formation and function. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses, moreover, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Together, these results suggest that Shh secreted from deep layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.

neuroscience↗

bioRxiv2018

Meiotic effects of MSH4 copy number variation support an adaptive role for post-polyploidy gene loss

Many eukaryotes descend from polyploid ancestors that experienced massive duplicate gene loss. This genomic erosion is particularly strong for duplicated (meiotic) recombination genes that return to a single copy more rapidly than genome average following polyploidy. To better understand the evolutionary forces underlying duplicate loss, we analysed how varying copy numbers of MSH4, an essential meiotic recombination gene, influences crossover formation in allotetraploid Brassica napus. We show that faithful chromosome segregation and crossover frequencies between homologous chromosomes are unchanged with MSH4 duplicate loss; by contrast, crossovers between homoeologous chromosomes (which result in genomic rearrangements) decrease with reductions in MSH4 copy number. We also found that inter-homoeologue crossovers originate almost exclusively from the MSH4-dependent crossover pathway. Limiting the efficiency of this pathway by decreasing the copy number of key meiotic recombination genes could therefore contribute to adaptation to polyploidy, by promoting regular chromosome segregation and genomic stability.

genetics↗