Biology subjects

Peruzza, L.

Publications and source records attributed to Peruzza, L..

6 recordsLinked to original sources

bioRxiv2026

MicroRNA modulation of viral nervous necrosis resistance in European seabass

MicroRNAs (miRNAs) are key post-transcriptional regulators of antiviral immunity, controlling gene expression by targeting 3 UTRs of immune-related transcripts. Despite their importance, the role of miRNAs in viral nervous necrosis (VNN) resistance in European seabass (Dicentrarchus labrax) is unexplored. Here, we characterized for the first time the brain miRNome of seabass from three VNN-resistance genotypes (susceptible, intermediate, resistant) across two genetically distinct seabass clusters. Differential expression analyses revealed cluster-specific patterns, with susceptible fish consistently showing overexpression of the differently expressed miRNAs (DEmiRNAs) as compared to the resistant fish. Considering the two genetic clusters in the study, miR-199-5p was differentially expressed between the VNN susceptible and resistant fish. This miRNA was found to be less expressed in the resistant individuals. Functional characterization of the miRNA predicted that it binds to two distinct miRNA recognition elements (MREs) within the ifi27l2a 3 UTR. These MREs flank a SNP (Chr3:10,082,380) previously associated with VNN survival. A strong negative correlation (r= -0.840) between miR-199-5p expression and ifi27l2a mRNA abundance further supports a post-transcriptional repression mechanism. Together, these results propose a regulatory model in which miR-199-5p modulates ifi27l2a expression, contributing to phenotypic variation in VNN resistance and positioning it as a promising biomarker for seabass aquaculture breeding.

genomics↗

bioRxiv2026

A dual-clam species 63K SNP array for sustainable production and conservation of wild resources

Bivalves play an essential role in coastal ecosystems and their aquaculture represents an important economic sector in Europe playing a pivotal role within the EU Blue Growth Strategy. Among clam species, the Manila clam, Ruditapes philippinarum, and the grooved carpet shell, R. decussatus, are within the top five species in terms of production volume and economic value. In this study we designed and validated the first medium-density 63K single nucleotide polymorphism (SNP) array for these two commercially important species. By leveraging a new chromosome-level genome assembly for R. philippinarum and that of R. decussatus, we identified over 300 million SNPs through whole-genome resequencing and genotyping-by-sequencing strategies. After stringent filtering, we selected 49,392 high-quality SNPs for R. philippinarum and 14,193 for R. decussatus to construct a dual-species array. Array validation was carried out by genotyping 384 individuals across multiple wild populations and hatchery samples, demonstrating excellent performance, with 67.7% and 67.5% of SNPs classified as high-quality polymorphic markers for R. philippinarum and R. decussatus, respectively. Minor allele frequency, missing data rate, and inter-marker distance met stringent quality thresholds, confirming the array robustness for clam population genetics. Parentage analysis in R. philippinarum families highlighted significant power for pedigree reconstruction in breeding programs. This publicly available genomic resource provides a reliable, cost-effective genotyping platform to enable population genomics and advanced selective breeding, genome-wide association studies, and genetic monitoring, ultimately strengthening management of genetic diversity and sustainable farming for two key clam species.

genomics↗

bioRxiv2025

Functional and molecular rescue of aganglionic colon by human enteric nervous system progenitor transplantation in Hirschsprung disease

Hirschsprung disease (HSCR) is a devastating congenital disorder characterised by absence of the enteric nervous system (ENS) in the distal gut. Cell therapy, using human pluripotent stem cell-derived ENS progenitors, offers an attractive alternative to treat this life-limiting disorder. Here we provide an in-depth characterisation of the HSCR phenotype in the B6;129-Ednrbtm1Ywa/J mouse model including molecular analyses highlighting the wide-ranging molecular effects of aganglionosis in HSCR colon. We show that transplantation of hPSC-derived ENS progenitors leads to significant increases in contractile function with formation of extensive donor-derived neuronal networks in colonic explants. Moreover, post-transplantation, we show that integration of ENS progenitors rescues many of the biological pathways impacted in the HSCR aganglionic microenvironment. These novel results provide strong evidence that human ENS progenitor transplantation can modulate critical signalling pathways affected in HSCR and exert positive impacts on contractile function, in aganglionic tissue, supporting further translational development of this regenerative medicine approach.

cell biology↗

bioRxiv2025

Purinergic signalling and calcium dynamics: potential drivers in the onset of coordinated intestinal motility in human fetal development

Background and aimsIntestinal motility relies on inputs from multiple cells within a complex neuromuscular syncytium located in the gut wall. While it is known that motility is dependent on the development of motor patterns which govern coordinated contractile activity within the gut wall, knowledge regarding the onset of coordinated motor activity in humans is still lacking. This study assessed the emergence of coordinated motor patterns, and the molecular mechanisms underpinning developing motility, in the human fetal gut. MethodsHuman fetal gut samples (obtained via the MRC-Wellcome Trust Human Developmental Biology Resource-UK) were characterised by live imaging, spatiotemporal mapping, immunohistochemistry and RNAseq. ResultsHuman small intestinal samples displayed the presence of key cell types including enteric neurons, interstitial cells of Cajal, platelet-derived growth factor receptor alpha positive (PDGFR+) cells and smooth muscle at post conception week (PCW) 12. Between PCW12 and PCW16, functional assessment revealed a marked increase in the velocity (p= 0.0341) of propagating contractions. Subsequently, between PCW16 and PCW20 the number of contraction initiation sites reduced drastically (p=0.0053), enabling the emergence of long-distance propagating contractions. Expression analyses showed the development of coordinated motor activity was coincident with increased expression of various genes involved in calcium and purinergic signalling pathways. ConclusionsThese findings provide the first direct mechanistic evidence of the temporal development of coordinated contractile activity in the human fetal intestine, highlighting the role of calcium dynamics, purinergic signalling and interstitial cells in early stages of human motility development, potentially informing an improved understanding of the pathogenesis of gut motility disorders.

developmental biology↗

bioRxiv2024

Integrated functional genomic analysis identifies the regulatory variants underlying a major QTL for disease resistance in European sea bass

BackgroundViral nervous necrosis (VNN) is a viral disease threatening the sustainability of global aquaculture, and affecting over 50 of farmed and ecologically important species. A major QTL for resistance to VNN has been previously described in European sea bass, but the underlying causal gene(s) and mutation(s) are unknown. To identify the mechanisms and genetic factors underpinning resistance to VNN, we integrated farmed and wild genetic data with multiple functional genomics assays in a farmed European sea bass population. ResultsA high heritability (h2 [~] 0.40) was estimated for VNN resistance. A major QTL for this trait was confirmed on chromosome 3, and whole-genome resequencing narrowed its location to a small region containing 4 copies of interferon alpha inducible protein 27-like 2A (IFI27L2A) genes, and one copy of the interferon alpha inducible protein 27-like 2 (IFI27L2) gene. RNA sequencing revealed a clear association between the QTL genotype and the expression of two of the IFI27L2A genes, and the IFI27L2 gene. Integration with chromatin accessibility and histone modification data pinpointed two SNPs in active regulatory regions of two of these genes (IFI27L2A and IFI27L2), and transcription factor binding site gains for the resistant alleles were predicted. These alleles, particularly the SNP variant CHR3:10077301, exhibited higher frequency in Eastern Mediterranean sea bass populations, which show considerably higher levels of resistance to VNN. ConclusionsThe SNP variant CHR3:10077301, through modulation of IFI27L2 and IFI27L2A genes, is likely the causative mutation underlying resistance to VNN in European sea bass. This is one of the first causative mutations discovered for disease resistance traits, and paves the way for marker-assisted selection as well as biotechnological approaches to enhance resistance to VNN in European sea bass and other susceptible species.

genetics↗

bioRxiv2024

Generating gnotobiotic bivalves: a new method on Manila clam (Ruditapes philippinarum)

The microbiome, which encompasses microbial communities associated with animal hosts, exerts a profound impact on host physiology and ecosystem dynamics. The application of advanced sequencing technologies has enabled researchers to investigate the composition of microbiomes across a range of hosts and environments. While correlating microbial composition with health outcomes has been a priority, interpreting such data requires caution to avoid overemphasizing the roles of microbes. Understanding microbial influence demands mechanistic insights, which are often elucidated through gnotobiology. Despite their limitations in representing animal diversity, model organisms offer the advantage of reproducibility and experimental tractability. However, the marine realm, especially bivalves, which are crucial for ecosystem functioning and aquaculture, lacks gnotobiotic models. In this study, we present a method for generating microbiome-depleted and gnotobiotic clams (Ruditapes philippinarum), one of the most widely farmed molluscs in the world and a sentinel organism for climate change. This model expands gnotobiotic research into marine invertebrates, thereby enabling investigations into the impact of microbes on such key animal species.

microbiology↗