Biology subjects

Mercurio, S.

Publications and source records attributed to Mercurio, S..

5 recordsLinked to original sources

bioRxiv2026

Proteome analysis reveals common players between the physiological neurodegeneration of the ascidian Ciona intestinalis and the pathological neurodegeneration in humans

Tunicates, including ascidians, are recognized as the true sister group of vertebrates and are emerging as models to study the development and degeneration of central nervous system (CNS). Ascidian larvae have the typical chordate body plan that includes a dorsal neural tube. During their metamorphosis, a deep tissue reorganization takes place, with some tissues that degenerate while others develop to become functional during the adult life. The larval CNS also degenerates and most neurons disappear, making room for the formation of adult CNS. The genome of the ascidian Ciona intestinalis has been sequenced and annotated, with several CNS specific genes that have been characterized, revealing specification mechanisms shared with humans. These features make ascidian metamorphosis a good model to study the mechanisms underlying physiological CNS degeneration and to compare them to the pathological conditions typical of neurodegenerative diseases. In order to shed light on the molecular determinants of C. intestinalis metamorphosis and neurodegeneration, we analyzed the proteome at three stages of development: swimming larva (SwL, Hotta stage 28), settled larva (SetL, Hotta stage 32) and metamorphosing larva (MetL, Hotta stage 34). A total of 405 modulated proteins were identified by mass spectrometry by comparing the three stages. Enrichment and network analysis showed the involvement of several processes/pathways, including autophagy and mTOR pathway, and actin cytoskeleton organization and remodeling among the most significant ones. This study elucidates molecular pathways underlying ascidian metamorphosis and highlights shared mechanisms between physiological neurodegeneration in ascidians and pathological neurodegeneration in humans.

neuroscience↗

bioRxiv2024

Bisphenol A affects the development and the onset of photosymbiosis in the acoel Symsagittifera roscoffensis

Photosymbiosis indicates a long-term association between animals and photosynthetic organisms. It has been mainly investigated in photosymbiotic cnidarians, while other photosymbiotic associations have been largely neglected. The acoel Symsagittifera roscoffensis lives in obligatory symbiosis with the microalgal Tetraselmis convolutae and has recently emerged as alternative model to study photosymbiosis. Here, we investigated the effects of Bisphenol A, a common plastic additive, on two pivotal stages of its lifecycle: aposymbiotic juvenile development and photosymbiogenesis. Based on our results, this pollutant altered the development of the worms and their capacity to engulf algae from the environment at concentrations higher than the levels detected in seawater, yet aligning with those documented in sediments of populated areas. Data provide novel information about the effects of pollutants on photosymbiotic associations and prompt the necessity to monitor their concentrations in marine environmental matrices.

zoology↗

bioRxiv2024

A feather star is born: embryonic development and nervous system organization in the crinoid Antedon mediterranea

BackgroundCrinoids belong to the phylum Echinodermata, marine invertebrates with a highly derived pentaradial body plan. As the only living members of the Pelmatozoa, the sister group to other extant echinoderms, crinoids are in a key phylogenetic position to reconstruct the evolutionary history of this phylum. However, the development of crinoids has been scarcely investigated, limiting their potential for comparative studies. Many crinoids are difficult to collect in the wild and embryo manipulation is challenging. Conversely, the Mediterranean feather star Antedon mediterranea can be found in shallow waters and has been used for experimental studies, most notably to investigate regeneration. ResultsThe aim here was to establish A. mediterranea as an experimental system for developmental biology. To accomplish this, we set up a method for culturing embryos in vitro from zygote to hatching larva stage that allowed us to define a developmental timeline and a standardized staging system for this species. We then optimized protocols to characterize the development of the main structures of the feather star body plan, using a combination of microscopy techniques and whole mount immunohistochemistry and in situ hybridization chain reaction. Focusing on the nervous system, we show that the larval apical organ includes a combination of serotonergic, GABAergic and glutamatergic neurons that form under the influence of a conserved anterior molecular signature. The larval neural plexus is instead composed of glutamatergic neurons and develops during the formation of the ciliary bands. Larval neurons disappear at metamorphosis, and the ectoneural and entoneural components of the adult nervous system develop early in post-metamorphic stages. Furthermore, the oral ectoderm that contains the ectoneural system acquires an "anterior" signature expressing Six3/6 and Lhx2/9 orthologs. ConclusionsOur results deepen our knowledge on crinoid development and provide new techniques to investigate feather star embryogenesis, promoting the use of A. mediterranea in developmental and evolutionary biology. This in turn will pave the way for the inclusion of crinoids in comparative studies to understand the origin of the echinoderm body plan and clarify many unanswered questions on deuterostome evolution.

developmental biology↗

bioRxiv2023

SOX2 and NR2F1 coordinate the gene expression program of the early postnatal visual thalamus

The thalamic dorsolateral geniculate nucleus, (dLGN) receives visual input from the retina via the optic nerve, and projects to the cortical visual area, where eye-derived signals are elaborated. The transcription factors SOX2 and NR2F1 are directly involved in the differentiation of dLGN neurons, based on mouse work and patient mutations leading to vision defects. However, whether they regulate each other, or control common targets is still unclear. By RNA-seq analysis of neonatal dLGN from thalamo-specific Sox2 and Nr2f1 mouse mutants, we found a striking overlap of deregulated genes. Among them, VGF, a cytokine transported along thalamic-cortical axons is strongly downregulated in both mutants. CUT&RUN analysis of SOX2 binding in dLGN chromatin identified a binding pattern characteristic of the dLGN. Collectively, the SOX2 and NR2F1- coregulated genes, and cognate SOX2 binding sites, contribute as a basis to understand the gene regulatory network driving the differentiation and connectivity of thalamic neurons.

developmental biology↗

bioRxiv2020

An early Sox2-dependent gene expression program required for hippocampal dentate gyrus development

The hippocampus is a brain area central for cognition. Mutations in the human SOX2 transcription factor cause neurodevelopmental defects, leading to intellectual disability and seizures, together with hippocampal dysplasia. We generated an allelic series of Sox2 conditional mutations in mouse, deleting Sox2 at different developmental stages. Late Sox2 deletion (from E11.5, via Nestin-Cre) affects only postnatal hippocampal development; earlier deletion (from E10.5, Emx1-Cre) significantly reduces the dentate gyrus, and the earliest deletion (from E9.5, FoxG1-Cre) causes drastic abnormalities, with almost complete absence of the dentate gyrus. We identify a set of functionally interconnected genes (Gli3, Wnt3a, Cxcr4, p73 and Tbr2), known to play essential roles in hippocampal embryogenesis, which are downregulated in early Sox2 mutants, and (Gli3 and Cxcr4) directly controlled by SOX2; their downregulation provides plausible molecular mechanisms contributing to the defect. Electrophysiological studies of the Emx1Cre mouse model reveal altered excitatory transmission in CA1 and CA3 regions.

developmental biology↗