Laurence, M. | Search bioRxiv

bioRxiv2026

Nuclear envelope-dependent heterochromatin positioning gates the timing of nucleolar assembly in the early embryo

The nucleolus is the largest nuclear condensate, yet how its assembly is developmentally timed remains poorly understood. In the Caenorhabditis elegans embryo, nucleoli normally appear at the 6- to 8-cell stage. Here we show that the LINC complex and nuclear lamina restrain premature nucleolar assembly through heterochromatin organization. Depletion of the embryonic LINC complex proteins SUN-1 or ZYG-12 induces precocious FIB-1-positive nucleoli at the 4-cell stage, particularly in the EMS and P2 blastomeres. LMN-1 depletion produces a more severe phenotype combining premature assembly with impaired disassembly. Loss of the heterochromatin anchor CEC-4 alone has modest effects but strongly suppresses precocious nucleolar assembly caused by LINC complex depletion. LINC complex and lamin perturbations alter the heterogeneity of HPL-2-marked chromatin, and FIB-1 condensates occupy locally HPL-2-depleted regions. These findings identify nuclear envelope-dependent heterochromatin organization as a developmental gate for nucleolar condensate assembly.

cell biology↗

bioRxiv2022

Antimicrobial susceptibility testing for diverse Malassezia species

The genus Malassezia is an opportunistic lipid-dependent yeast that is associated with common skin diseases and has recently been associated with Crohns disease and certain cancers. Understanding the susceptibility of Malassezia to diverse antimicrobial agents is crucial for identifying effective antifungal therapies. Here, we tested the efficacy of isavuconazole, itraconazole, terbinafine and artemisinin against three Malassezia species: M. restricta, M. slooffiae, and M. sympodialis, using microbroth dilution techniques. We found antifungal properties for the two previously-unstudied antimicrobials: isavuconazole and artemisinin. Overall all Malassezia species were particularly susceptible to itraconazole, with a MIC range from 0.0015 to 0.1562 M. ImportanceThe Malassezia genus is known to be a cause of skin conditions and has recently been associated with diseases such as Crohns disease, pancreatic ductal carcinoma and breast cancer. This work was completed to assess the susceptibility to a variety of antimicrobial drugs on diverse Malassezia species, in particular Malassezia restricta.

microbiology↗

bioRxiv2019

Disentangling group specific QTL allele effects from genetic background epistasis using admixed individuals in GWAS: an application to maize flowering

When handling a structured population in association mapping, group-specific allele effects may be observed at quantitative trait loci (QTLs) for several reasons: (i) a different linkage disequilibrium (LD) between SNPs and QTLs across groups, (ii) group-specific genetic mutations in QTL regions, and/or (iii) epistatic interactions between QTLs and other loci that have differentiated allele frequencies between groups. We present here a new genome-wide association (GWAS) approach to identify QTLs exhibiting such group-specific allele effects. We developed genetic materials including admixed progeny from different genetic groups with known genome-wide ancestries (local admixture). A dedicated statistical methodology was developed to analyze pure and admixed individuals jointly, allowing one to disentangle the factors causing the heterogeneity of allele effects across groups. This approach was applied to maize by developing an inbred \"Flint-Dent\" panel including admixed individuals that was evaluated for flowering time. Several associations were detected revealing a wide range of configurations of allele effects, both at known flowering QTLs (Vgt1, Vgt2 and Vgt3) and new loci. We found several QTLs whose effect depended on the group ancestry of alleles while others interacted with the genetic background. The existence of directional epistasis was highlighted by comparing admixed with pure individuals and was consistent with epistatic interactions identified at the level of QTLs. Our GWAS approach provides useful information on the stability of QTL effects across genetic groups and can be applied to a wide range of species.\n\nAuthor summaryIdentification of genomic regions involved in genetic architecture of traits has become commonplace in quantitative genetics studies. Genetic structure is a common feature in human, animal and plant species and most current methods target genomic regions whose effects on traits are conserved between genetic groups. However, a heterogeneity of allele effects may be observed due to different factors: a group-specific correlation between the alleles of the tagged marker and those of the causal variant, a group-specific mutation at the causal variant or an epistatic interaction between the causal variant and the genetic background. We propose a new method adapted to structured populations including admixed individuals, which aims to identify these genomic regions and to unravel the previous factors. method was applied to a maize inbred diversity panel including lines from the dent and the flint genetic groups, as well as admixed lines, evaluated for flowering time. Several genomic regions were detected with various configurations of allele effects, with evidence of epistatic interactions between some of the loci and the genetic background.

genetics↗