Studies on axial elongation and segmentation in vertebrate embryos

The vertebrate body is segmented along the anteroposterior axis into repetitive structures, the vertebrae, which derive from embryonic precursors called somites. During development, periodic somite formation is driven by a molecular oscillator, the segmentation clock. Segmentation and elongation of the body axis depend on a population of progenitor cells located at the tail end of the embryo that contributes to axial tissues, including somitic tissue, until the entire embryonic body and the correct number of somites is produced. Although much is known about somite production, it is not known how segmentation and axial elongation come to an end. In this thesis, I show that termination of chick axial elongation is associated with decline of signals required for maintenance of progenitor cells, implying that downregulation of these signals triggers depletion of the progenitors. I also show that somite formation decreases as axial elongation comes to an end, suggesting that slow down of the segmentation clock causes somite formation to cease. I have also explored whether the dose of specific genes is limiting in determining the final somite number in mouse, and I have found that heterozygous mutations of selected genes of the Wnt signalling pathway form fewer somites, indicating that Wnt gene activity might be limiting in controlling the definitive somite number. I have also investigated the role of Greb1, a gene that our laboratory identified as being selectively expressed in the tail region where progenitors reside. I provide evidence that Greb1 controls axial morphogenesis of the zebrafish embryo by regulating movements required for normal convergence and extension of the embryonic axis during gastrulation. My results possibly provide a link between progenitor contribution to axial elongation and cell movements in the tail

Greb1 is required for axial elongation and segmentation in vertebrate embryos

During vertebrate embryonic development, the formation of axial structures is driven by a population of stem-like cells that reside in a region of the tailbud called the chordoneural hinge (CNH). We have compared the CNH transcriptome with those of surrounding tissues and shown that the CNH and tailbud mesoderm are transcriptionally similar, and distinct from the presomitic mesoderm. Amongst CNH-enriched genes are several that are required for axial elongation, including Wnt3a, Cdx2, Brachyury/T and Fgf8 , and androgen/estrogen receptor nuclear signalling components such as Greb1 . We show that the pattern and duration of tailbud Greb1 expression is conserved in mouse, zebrafish, and chicken embryos, and that Greb1 is required for axial elongation and somitogenesis in zebrafish embryos. The axial truncation phenotype of Greb1 morphant embryos is explained by much reduced expression of No tail ( Ntl/Brachyury ) which is required for axial progenitor maintenance. Posterior segmentation defects in the morphants (including misexpression of genes such as mespb, myoD and papC ) appear to result, in part, from lost expression of the segmentation clock gene, her7

L\u2019uso dei dati di posizionamento e i ritmi di attivit\ue0 per la gestione conservativa dell\u2019Orso nell\u2019area compresa tra il Friuli Orientale e la Slovenia

5openopenCABONI A; VEZZARO S; SALERNO B; FATTORI U; FILACORDA SCaboni, A; Vezzaro, S; Salerno, B; Fattori, U; Filacorda, Stefan

Covid-19 patient management in outpatient setting: A population-based study from southern italy

Evidence on treatments for early-stage COVID-19 in outpatient setting is sparse. We explored the pattern of use of drugs prescribed for COVID-19 outpatients’ management in Southern Italy in the period February 2020–January 2021. This population-based cohort study was conducted using COVID-19 surveillance registry from Caserta Local Health Unit, which was linked to claims databases from the same catchment area. The date of SARS-CoV-2 infection diagnosis was the index date (ID). We evaluated demographic and clinical characteristics of the study drug users and the pattern of use of drugs prescribed for outpatient COVID-19 management. Overall, 40,030 patients were included in the analyses, with a median (IQR) age of 44 (27–58) years. More than half of the included patients were asymptomatic at the ID. Overall, during the study period, 720 (1.8%) patients died due to COVID-19. Azithromycin and glucocorticoids were the most frequently prescribed drugs, while oxygen was the less frequently prescribed therapy. The cumulative rate of recovery from COVID-19 was 84.2% at 30 days from ID and it was lower among older patients. In this study we documented that the drug prescribing patterns for COVID-19 treatment in an outpatient setting from Southern Italy was not supported from current evidence on beneficial therapies for early treatment of COVID-19, thus highlighting the need to implement strategies for improving appropriate drug prescribing in general practice