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Vazquez-Marin, J.

Publications and source records attributed to Vazquez-Marin, J..

3 recordsLinked to original sources

Spatial transcriptomics map of the embryonic mouse brain: a tool to explore neurogenesis

The developing brain has a well-organized anatomical structure comprising different types of neural and non-neural cells. Stem cells, progenitors, and newborn neurons tightly interact with their neighbouring cells and tissue microenvironment, and this intricate interplay ultimately shapes the output of neurogenesis. Given the relevance of spatial cues during brain development, we acknowledge the necessity for a spatial transcriptomics map accessible to the neurodevelopmental community. To fulfil this need, we generated spatially-resolved RNAseq data from E13.5 mouse brain sections immunostained for mitotic active neural and vascular cells. Unsupervised clustering defined specific cell type populations of diverse lineages and differentiation states. Differential expression analysis revealed unique transcriptional signatures across specific brain areas, uncovering novel features inherent to particular anatomical domains. Finally, we integrated existing single-cell RNAseq datasets into our Spatial Transcriptomics map, adding tissue context to single-cell RNAseq data. In summary, we provide a valuable tool that enables the exploration and discovery of unforeseen molecular players involved in neurogenesis, particularly in the crosstalk between different cell types. Summary StatementDi Marco, Vazquez-Marin et al. provide an open-access spatial transcriptomics atlas of the embryonic mouse brain. This spatial map enables the exploration and discovery of gene functions within tissue context.

neuroscience↗

Evolutionary conservation of embryonic DNA methylome remodelling in distantly related teleost species

Methylation of cytosines in the CG context (mCG) is the most abundant DNA modification in vertebrates that plays crucial roles in cellular differentiation and identity. After fertilization, DNA methylation patterns inherited from parental gametes are remodelled into a state compatible with embryogenesis. In mammals, this is achieved through the global erasure and re-establishment of DNA methylation patterns. However, in non-mammalian vertebrates like zebrafish, no global erasure has been observed. To investigate the evolutionary conservation and divergence of DNA methylation remodelling in teleosts, we generated base resolution DNA methylome datasets of developing medaka and medaka-zebrafish hybrid embryos. In contrast to previous reports, we show that medaka display comparable DNA methylome dynamics to zebrafish with high gametic mCG levels (sperm: [~]90%; egg: [~]75%), and adoption of a paternal-like methylome during early embryogenesis, with no signs of prior DNA methylation erasure. We also demonstrate that non-canonical DNA methylation (mCH) reprogramming at TGCT tandem repeats is a conserved feature of teleost embryogenesis. Lastly, we find remarkable evolutionary conservation of DNA methylation remodelling patterns in medaka-zebrafish hybrids, indicative of compatible DNA methylation maintenance machinery in far-related teleost species. Overall, these results suggest strong evolutionary conservation of DNA methylation remodelling pathways in teleosts, which is distinct from the global DNA methylome erasure and reestablishment observed in mammals.

developmental biology↗

A Yap-dependent transcriptional program directs cell migration for embryo axis assembly

The condensation of the embryo primary axis is a fundamental landmark in the establishment of the vertebrate body plan. Although the complex morphogenetic movements directing cell convergence towards the midline have been described extensively, little is known on how gastrulating cells interpret mechanical cues. Yap proteins are among the best characterized transcriptional mechanotransducers, yet their role in gastrulation has remained elusive. Here we show that the double knockout of yap and its paralog yap1b in medaka results in an axis assembly failure. Quantitative live imaging reveals that mutant cells display reduced displacement and migratory persistence. By characterizing the Yap-dependent transcriptional program, we identified genes involved in cytoskeletal organization and cell-ECM adhesion, rather than in germ layer specification, as direct Yap targets. Dynamic analysis of Tead sensors and downstream targets reveals Yap is acting in migratory cells, and not as a midline beacon, to direct gastrulating precursors trajectories by promoting cortical actin recruitment and focal adhesions assembly. We propose that Yap is engaged in a mechano-regulatory loop that is essential to maintain the directed cell migration sustaining embryo axis formation.

developmental biology↗