Biology subjects

Messina, G.

Publications and source records attributed to Messina, G..

3 recordsLinked to original sources

bioRxiv2022

Pangenomics provides insights into the role of synanthropy in barn swallow evolution

Insights into the evolution of non-model organisms are often limited by the lack of reference genomes. As part of the Vertebrate Genomes Project, we present a new reference genome and a pangenome produced with High-Fidelity long reads for the barn swallow Hirundo rustica. We then generated a reference-free multialignment with other bird genomes to identify genes under selection. Conservation analyses pointed at genes enriched for transcriptional regulation and neurodevelopment. The most conserved gene is CAMK2N2, with a potential role in fear memory formation. In addition, using all publicly available data, we generated a comprehensive catalogue of genetic markers. Genome-wide linkage disequilibrium scans identified potential selection signatures at multiple loci. The top candidate region comprises several genes and includes BDNF, a gene involved in stress response, fear memory formation, and tameness. We propose that the strict association with humans in this species is linked with the evolution of pathways typically under selection in domesticated taxa.

genomics↗

bioRxiv2021

Selective ablation of Nfix in Macrophages preserves Muscular Dystrophy by inhibiting FAPs-dependent fibrosis

Muscular dystrophies are genetic diseases characterized by chronic inflammation and fibrosis. Macrophages are immune cells that sustain muscle regeneration upon acute injury but seem deleterious in the context of chronic muscle injury such as muscular dystrophies. Here we observed that the number of macrophages expressing the transcription factor Nfix increases in two distinct murine models of muscular dystrophies. Plus, we showed that the deletion of Nfix in macrophages in dystrophic mice delays fibrosis establishment and muscle wasting until 6 months of life. Indeed, macrophages lacking Nfix express more TNF and less TGF{beta}1 thus promoting apoptosis of fibro-adipogenic progenitors. Moreover, pharmacological treatment of dystrophic mice with ROCK inhibitor accelerates fibrosis through the increase of Nfix expression by macrophages. Thus, we identify Nfix as a macrophage profibrotic actor in muscular dystrophies, whose inhibition could be a therapeutic way to rescue the dystrophic disease.

cell biology↗

bioRxiv2020

ATPase SRCAP is a new player in cell division, uncovering molecular aspects of Floating-Harbor syndrome

Floating-Harbor syndrome (FHS) is a rare genetic disease affecting human development caused by heterozygous truncating mutations in the Srcap gene, which encodes the ATPase SRCAP, the core catalytic subunit of the homonymous chromatin-remodeling complex. Using a combined approach, we studied the involvement of SRCAP protein in cell cycle progression in HeLa cells. In addition to the canonical localization in interphase nuclei, both SRCAP and its Drosophila orthologue DOMINO-A localized to the mitotic apparatus after nuclear envelope breakdown. Moreover, SRCAP and DOMINO-A depletion impaired mitosis and cytokinesis in human and Drosophila cells, respectively. Importantly, SRCAP interacted with several cytokinesis regulators at telophase, strongly supporting a direct role in cytokinesis, independent of its chromatin remodeling functions. Our results provide clues about previously undetected, evolutionarily conserved roles of SRCAP in ensuring proper mitosis and cytokinesis. We propose that perturbations in cell division contribute to the onset of developmental defects characteristic of FHS. SummaryO_ST_ABSSignificance statementC_ST_ABSSrcap is the causative gene of the rare Floating Harbor syndrome (FHS). It encodes the ATPase SRCAP, the core catalytic subunit of the homonymous multiprotein chromatin-remodeling complex in humans, which promotes the exchange of canonical histone H2A with the H2A.Z variant. According to the current view on SRCAP protein functions, FHS is caused by chromatin remodeling defects. Our findings suggest that, in addition to the established function as epigenetic regulator, SRCAP plays previously undetected and evolutionarily conserved roles in cell division. Hence, we propose that perturbations in cell division produced by SRCAP mutations are important causative factors co-occurring at the onset of FHS.

cell biology↗