Biology subjects

Mora, P.

Publications and source records attributed to Mora, P..

6 recordsLinked to original sources

bioRxiv2024

Sex chromosome turnover in African annual killifishes of the genus Nothobranchius

Sex chromosomes of teleost fishes often have low levels of differentiation and undergo frequent turnovers. Annual Nothobranchius killifishes comprise representatives with male-heterogametic XY or X1X2Y sex chromosome systems, scattered across their phylogeny, nested within species lacking cytologically detectable sex chromosomes. They thus provide a suitable system to study sex chromosome evolution and turnover. Here, we combined molecular cytogenetics and genomic analyses to examine several multiple sex chromosome systems in Nothobranchius spp. and their outgroup Fundulosoma thierryi. We used fluorescence in situ hybridization with three sex chromosome-specific painting probes and bacterial artificial chromosomes (BAC) bearing eight orthologues of genes found to be repeatedly co-opted as master sex determining (MSD) genes in fishes. Our results suggest at least four independent origins of sex chromosomes in the genus Nothobranchius. The synteny block carrying amhr2 gene was shared by X1X2Y systems of N. brieni, N. guentheri and N. lourensi, but the autosomal additions and the overall neo-Y chromosome structure differed among these species. On the other hand, gdf6 gene was localized to neo-Y of F. thierryi. None of the mapped MSD gene candidates seems to determine sex in N. ditte. We further sequenced genomes of F. thierryi female and N. guentheri male by long-read platforms and performed analyses of male and female Pool-seq data and coverage to delimit their non-recombining regions, determine degree of their differentiation, and thus complement the cytogenetic data in assessing potential MSD genes. We found low level of sex chromosomes differentiation in F. thierryi. In N. guentheri, however, we identified two distinct evolutionary strata on neo-Y. The amhr2 gene resides in the younger stratum and has low allelic variation, which questions its role in sex determination.

evolutionary biology↗

bioRxiv2024

Community density patterns estimated by species distribution modeling: the case study of an insect virus interaction

O_LITime delays complicates the analysis of trophic dependence, which requires large time series data to study local associations. C_LIO_LIHere we propose using species distribution modeling. This approach removes confounding time lag effects and allows using data obtained separately in the different species. C_LIO_LISince the approach is correlative, it cannot be interpreted in terms of causality. C_LIO_LIWe apply the method to the interaction between the invasive potato moth Tecia solanivora and its granulovirus PhoGV in the Northern Andes. Host density was analyzed based on 1206 pheromone trap data from 106 sampled sites in Ecuador, Colombia and Venezuela. Virus prevalence was evaluated in 15 localities from 3 regions in Ecuador and Colombia. glm models were optimized for both variables on bioclimatic variables. Predicted virus prevalence was not significantly correlated to host density in the sampled virus sites. Across the climatic range covered by the study, correlation was R=-0.053. Of the total population of insect in this range, 26% were expected to be infected. C_LIO_LIInfection status was also analyzed for spatial structure at different scales: storage bag, storage room, field, locality, country. Locality and storage bag explained respectively 8% and 26% of the total deviance in infection status in glm analysis. Field and storage structure differed within locality but not always in the same direction. C_LIO_LIThis basic method may help studying statistical relationships between species density across a number of trophic models making use of existing non sympatric data, with none or limited additional sampling effort. C_LI

ecology↗

bioRxiv2023

Juxtacrine DLL4-NOTCH1 signaling between astrocytes drives neuroinflammation via the IL-6-STAT3 axis

Under neuroinflammatory conditions, astrocytes acquire a reactive phenotype that drives acute inflammatory injury as well as chronic neurodegeneration. We hypothesized that astrocytic DLL4 may interact with its receptor NOTCH1 on neighboring astrocytes to regulate astrogliosis via downstream juxtacrine signaling pathways. Here we investigated the role of astrocytic DLL4 on neurovascular unit homeostasis under neuroinflammatory conditions. We probed for downstream effectors of the DLL4-NOTCH1 axis and targeted these for therapy in two models of CNS inflammatory disease. We first demonstrated that astrocytic DLL4 is upregulated during neuroinflammation, both in mice and humans, driving astrogliosis and subsequent blood brain barrier permeability and inflammatory infiltration. We then showed that the DLL4-mediated NOTCH1 signaling in astrocytes directly drives IL-6 levels, induces STAT3 phosphorylation promoting upregulation of astrocyte reactivity markers, pro-permeability factor secretion and consequent blood brain barrier destabilization. Finally we revealed that blocking DLL4 with antibodies improves experimental autoimmune encephalomyelitis symptoms in mice, identifying a potential novel therapeutic strategy for CNS autoimmune demyelinating disease. As a general conclusion, this study demonstrates that DLL4-NOTCH1 signaling is not only a key pathway in vascular development and angiogenesis, but also in the control of astrogliosis during neuroinflammation.

neuroscience↗

bioRxiv2023

Fast centromeric repeat turnover provides a glimpse into satellite DNA evolution in Nothobranchius annual killifishes

Satellite DNA (satDNA) is rapidly evolving class of tandem repeats with some motifs being involved in centromere organization and function. Rapid co-evolution of centromeric satDNA and associated proteins has been mostly attributed to the so-called centromere drive. To identify repeats associated with centromeric regions and test for the role of meiotic drive in their evolution, we investigated satDNA across Southern and Coastal clades of African annual killifishes of the genus Nothobranchius. C-banding showed expansion of (peri)centromeric heterochromatin regions in the Southern-clade killifishes. Molecular cytogenetic and bioinformatic analyses further revealed that two previously identified satellites, Nfu-SatA and Nfu-SatB, are associated with centromeres only in one lineage of the Southern clade. Nfu-SatB was, however, detected outside centromeres also in other members of the Coastal clade, which is consistent with the "library" hypothesis of satDNA evolution. We also identified a novel satDNA, Cl-36, associated with (peri)centromeres in N. foerschi, N. guentheri and N. rubripinnis from the Coastal clade. Our findings could be explained by centromere drive shaping karyotype change and centromeric repeat turnover in Nothobranchius species with possible reversal of spindle polarity within the Southern clade.

genetics↗

bioRxiv2023

Increased endothelium activation and leakage do not promote diastolic dysfunction in mice fed with a high fat diet and treated with L-NAME

Coronary microvascular disease has been proposed to be responsible for heart failure with preserved ejection fraction (HFpEF) about 10 years ago. However, to date the role and phenotype of the coronary microvasculature has still been poorly considered and investigated in animal models of HFpEF. ObjectiveTo determine whether endothelial dysfunction participates in the development of diastolic dysfunction in mice fed with a high fat diet (HDF) and treated with L-NAME. Approach and ResultsAt first, we thoroughly phenotyped the coronary microvasculature in this model in male, female and ovariectomized (OVX) female considering the sexual dimorphism associated with this disease. We found that both OVX and non OVX females but not males display increased endothelial activation, leakage, and arteriole constriction upon the HFD + L-NAME regimen while both male and OVX females but not non OVX females develop diastolic dysfunction. With the aim to investigate the role of endothelial dysfunction in the pathophysiology of diastolic dysfunction in OVX female mice, we used Cdon deficient mice. Indeed, we previously demonstrated that endothelium integrity, upon inflammatory conditions, is preserved in these mice. Both OVX Cdh5-Cre/ERT2-CdonFlox/Flox (CdonECKO) and CdonFlox/Flox (Ctrl) female mice were fed with the HFD + L-NAME regimen to induced diastolic dysfunction. As expected, CdonECKO mice displayed improved endothelium integrity i.e. decreased endothelium permeability, decreased ICAM-1 expression and decreased infiltration of CD45+ leukocytes in comparison to control mice. However, CdonECKO mice displayed cardiac hypertrophy, cardiac fibrosis and increased end diastolic pressure just like control mice. Moreover, we found that cardiac inflammation does not participate in the pathophysiology of HFpEF either by treating OVX female mice with colchicine. ConclusionAltogether, the data presented in this paper demonstrate that neither endothelium permeability nor endothelial activation or inflammation do participate in the pathophysiology of diastolic dysfunction in mice exposed to HFD+L-NAME.

pathology↗

bioRxiv2020

Genetic disruption of the Blood Brain Barrier leads to protective barrier formation at the Glia Limitans

Recent work demonstrated that Central Nervous System (CNS) inflammation induces endothelial Blood Brain Barrier (BBB) opening as well as the formation of a tight junction barrier between reactive astrocytes at the Glia Limitans. We hypothesized that these two barriers may be reciprocally regulated by each other state and further, that the CNS parenchyma may acquire protection from the reactive astrocytic Glia Limitans not only in neuro-inflammation but also when BBB integrity is compromised under resting condition, without pathology. Previous studies identified Sonic hedgehog (Shh) astrocytic secretion as implicated in stabilizing the BBB during neuropathology and we recently demonstrated that desert hedgehog (Dhh) is expressed at the BBB in adults. Here we unraveled the role of the morphogen Dhh in maintaining BBB tightness and, using endothelial Dhh knockdown as a model of permeable BBB, we demonstrated that a double barrier system comprising both the BBB and Glia Limitans, is implemented in the CNS and regulated by a crosstalk going from endothelial cell to astrocytes. First, we showed that, under neuro-inflammatory conditions, Dhh expression is severely down regulated at the BBB and that Dhh is necessary for endothelial intercellular junction integrity as Dhh knockdown leads to CNS vascular leakage. We then demonstrated that, in Dhh endothelial knockout (DhhECKO) mice which display an open BBB, astrocytes are reactive and express the tight junction Claudin 4 (Cldn4) and showed that astrocytes can respond to signals secreted by the permeable endothelial BBB by becoming reactive and expressing Cldn4. To examine the consequences of the above results on disease severity, we finally induced multiple sclerosis in DhhECKO mice versus control littermates and showed that the pathology is less severe in the knockout animals due to Glia Limitans tightening, in response to BBB leakage, which drives inflammatory infiltrate entrapment into the perivascular space. Altogether these results suggest that genetic disruption of the BBB generates endothelial signals capable of driving the implementation of a secondary barrier at the Glia Limitans to protect the parenchyma. The concept of a reciprocally regulated CNS double barrier system has implications for treatment strategies in both the acute and chronic phases of multiple sclerosis pathophysiology.

neuroscience↗