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Abril, J. F.

Publications and source records attributed to Abril, J. F..

3 recordsLinked to original sources

Flavins in Focus: Vitamin B2 as a Metabolic Keystone for Neuronal Repair in Regenerating Planarians

Regeneration imposes substantial metabolic demands to support the reconstruction of functional tissues. Essential vitamins are indispensable metabolic cofactors, yet whether their availability is spatially organized to support local metabolic demands within regenerative tissues remains largely unknown. Here, we identify previously undescribed flavin-rich cells, referred to as 'flavinocytes', that form an extensive network that spatially organizes vitamin B2 metabolism in the planarian Schmidtea mediterranea. Using endogenous flavin autofluorescence as a label-free in vivo metabolic readout, we show that this network consists of elongated cells that form longitudinal varicosity-containing strands closely associated with the central nervous system. RNAi-mediated disruption of riboflavin uptake and metabolism reduced flavin-associated autofluorescence and its spatial distribution within the animal, while affecting blastema formation, eye regeneration, and nervous system reconstruction. These findings demonstrate that riboflavin metabolism is required for successful regeneration. Single-cell transcriptomics, protein localization, and functional perturbations further suggest a reciprocal relationship between flavinocytes and the regenerating nervous system, pointing to coordinated neuro-metabolic interactions during tissue repair. Together, our findings demonstrate the importance of riboflavin metabolism for nervous system regeneration and provide new insight into the spatial organization of metabolism during tissue regeneration.

developmental biology↗

Gene regulatory dynamics during the development of a paleopteran insect, the mayfly Cloeon dipterum

The evolution of insects has been marked by the appearance of key body plan innovations and novel organs that promoted the outstanding ability of this lineage to adapt to new habitats, boosting the most successful radiation in animals. To understand the origin and evolution of these new structures, it is essential to investigate which are the genes and gene regulatory networks participating during the embryonic development of insects. Great efforts have been made to fully understand, from a gene expression and gene regulation point of view, the development of holometabolous insects, in particular Drosophila melanogaster, with the generation of numerous functional genomics resources and databases. Conversely, how hemimetabolous insects develop, and which are the dynamics of gene expression and gene regulation that control their embryogenesis, are still poorly characterized. Therefore, to provide a new platform to study gene regulation in insects, we generated ATAC-seq (Assay for transposase-Accessible Chromatin using sequencing) for the first time during the development of the mayfly Cloeon dipterum. This new available resource will allow to better understand the dynamics of gene regulation during hemimetabolan embryogenesis, since C. dipterum belongs to the paleopteran order of Ephemeroptera, the sister group to all other winged insects. These new datasets include six different time points of its embryonic development and identify accessible chromatin regions corresponding to both general and stage-specific promoters and enhancers. With these comprehensive datasets, we characterised pronounced changes in accessible chromatin between stages 8 and 10 of embryonic development, which correspond to the transition from the last stages of segmentation to organogenesis and appendage differentiation. The application of ATAC-seq in mayflies has contributed to identify the epigenetic mechanisms responsible for embryonic development in hemimetabolous insects and it will provide a fundamental resource to understand the evolution of gene regulation in winged insects.

genomics↗

Genomic analyses reveal FoxG as an upstream regulator of wnt1 required for posterior identity specification in planarians

Embryonic specification of the first body axis requires the formation of an Organizer, a group of cells with the ability to instruct fates in the surrounding tissue. The existence of organizing regions in adults, i.e. during regeneration, which also requires patterning of new tissues, remains unstudied. To that aim, we study regeneration in planarians, flatworms that can regenerate any missing structure, even the head, in a few days. In planarians, as described in embryonic models, the cWNT pathway specifies the anterior-posterior axis. During the first 12-24h after amputation both wnt1 and notum (a Wnt inhibitor) are expressed in any wound, but 48 hours later they become restricted to posterior or anterior facing wounds, forming the anterior and the posterior organizers, respectively. In this study we undertook a genomic approach to further understand the mechanism that triggers the early expression of wnt1 and the specification of the posterior identity. Through ATAC-sequencing and CHIPmentation techniques we uncovered Cis-Regulatory Elements of Schmidtea mediterranea genome and analyzed them in notum and wnt1 (RNAi) animals. The result shows that already at 12 hours after amputation the chromatin structure of the wounds has changed its conformation according to the polarity of the pre-existing tissue. Analysing the DNA binding motives present in the proximal regulatory regions of genes down-regulated after wnt1 (RNAi) we found a few genes containing a TCF binding site, which include posterior Homeobox genes and chromatin remodelling proteins, suggesting that those are direct targets of the cWNT pathway and the responsible to trigger the expression of the posterior effectors. Furthermore, we have identified FoxG as an up-stream regulator of wnt1 transcription, probably though binding to an enhancer found in its first intron. Silencing of foxG inhibits the early phase of wnt1 expression and phenocopies the wnt1 (RNAi) phenotype, indicating its early role in specifying posterior versus anterior identity. Moreover, we have created a new open platform to interpret all transcriptomic and genomic results obtained (https://compgen.bio.ub.edu/PlanNET/planexp).

developmental biology↗