Search bioRxiv⌕ Search

Biology subjects

Sanchez, J. A.

Publications and source records attributed to Sanchez, J. A..

8 recordsLinked to original sources

A shared extracellular plasticity program drives brain repair and tumor progression

Injury induces complex multicellular repair responses that restore tissue integrity and replenish lost cells. In the brain, regeneration is limited and depends on the proliferation of neural and glial progenitors. But how these cells remodel the microenvironment to support repair remains poorly understood. Here, we profile dividing cells in the injured fruit fly brain revealing signatures of neural stem cell activation and ECM remodeling. We find that rapid activation of a Heparan Sulfate-binding factor (Hpsl) and changes in glypicans condition the extracellular space for proliferation. Hpsl promotes signalling of scarce Dpp/BMP ligands in brain cells with latent proliferative capacity and regulates organismal resilience to brain injury. We further show that malignant cells in fly and mouse brains promote similar HS-interactions to support tumor progression. Together, our findings identify extracellular proteoglycan remodeling as a key regulator of brain repair and uncover a common plasticity program engaged by brain damage and tumorigenesis.

cell biology↗

Diversity and distribution of the coral-associated endolithic algae Ostreobium in the Southwestern Caribbean

Coral reefs are facing significant environmental challenges. Ocean acidification has the potential to induce the dissolution of coral reefs. The community of micro-bioerosion exhibits a heightened level of concern in the context of ocean acidification. Comprehending the close interplay between bioeroders and corals is of utmost importance in predicting the trajectory of these vulnerable ecosystems. The genus Ostreobium, which belongs to the order Bryopsidales (Chlorophyta) and comprises euendolithic chlorophyte algae, has been identified as the primary cause of reef dissolution among microbioeroders. The objective of this study was to comprehend the inherent distribution of rbcL clades of Ostreobium in the Southwestern Caribbean corals within a gradient of reef depth. The Ostreobium rbcL variants were found to be linked with corals belonging to the Agariciidae, Merulinidae, Poritiidae, Siderastreidae, Astroconeiidae, Montastreidae, Mussidae, and Pocilloporidae families. The individuals selected for the current investigation are categorized as members of either the "complex" or "robust" coral groups. Our findings indicate that solely the corals categorized as complex exhibit close memberships with the three Ostreobium superclades. In general, the dispersion of Ostreobium within the Southwestern Caribbean region exhibits differentiation among various coral groups and is influenced by geographical and bathymetric factors. The Ostreobiums diversity is primarily composed of ecological specialists, wherein most clades are linked to particular hosts. Conversely, only a few ecological generalists are associated with multiple hosts, akin to zooxanthellae. Ostreobium exhibits greater diversity on encrusting corals such as agariciids, which are among the most abundant and widespread coral species in the Caribbean.

evolutionary biology↗

Myc-regulated miRNAs modulate p53 expression and impact animal survival under nutrient deprivation

The conserved transcription factor Myc regulates cell growth, proliferation and apoptosis, and its deregulation has been associated with human pathologies. Although specific miRNAs have been identified as fundamental components of the Myc tumorigenic program, how Myc regulates miRNA biogenesis remains controversial. Here we showed that Myc functions as an important regulator of miRNA biogenesis in Drosophila by influencing both miRNA gene expression and processing. Through the analysis of ChIP-Seq datasets, we discovered that nearly 56% of Drosophila miRNA genes show dMyc binding, exhibiting either the canonical or non-canonical E-box sequences within the peak region. Consistently, reduction of dMyc levels resulted in widespread downregulation of miRNAs gene expression. dMyc also modulates miRNA processing and activity by controlling Drosha and AGO1 levels through direct transcriptional regulation. By using in vivo miRNA activity sensors we demonstrated that dMyc promotes miRNA-mediated silencing in different tissues, including the wing primordium and the fat body. We also showed that dMyc-dependent expression of miR-305 in the fat body modulates Dmp53 levels depending on nutrient availability, having a profound impact on the ability of the organism to respond to nutrient stress. Indeed, dMyc depletion in the fat body resulted in extended survival to nutrient deprivation which was reverted by expression of either miR-305 or a dominant negative version of Dmp53. Our study reveals a previously unrecognized function of dMyc as an important regulator of miRNA biogenesis and suggests that Myc-dependent expression of specific miRNAs may have important tissue-specific functions.

developmental biology↗

Global phylogenomic assessment of Leptoseris and Agaricia reveals substantial undescribed diversity at mesophotic depths

Mesophotic coral communities are increasingly gaining attention for the unique biological species they host, exemplified by the numerous mesophotic fish species that continue to be discovered. In contrast, many of the photosynthetic scleractinian corals observed at mesophotic depths are assumed to be depth-generalists, with very few species characterised as mesophotic-specialists. This presumed lack of a specialised community remains largely untested, as phylogenetic studies rarely include mesophotic samples and have long suffered from resolution issues associated with traditional sequence markers. Here, we used reduced-representation genome sequencing to provide a phylogenomic assessment of the two dominant mesophotic genera of plating corals in the Indo-Pacific and Western Atlantic, respectively, Leptoseris and Agaricia. While these genome-wide phylogenies broadly corroborated the morphological taxonomy, they also exposed substantial undescribed diversity (at least 24 molecular clades across the 8 species), including deep divergences within genera and current taxonomic species. Five of the eight focal species consisted of at least two sympatrically-occurring, genetically distinct clades, which were consistently detected across different methods. The repeated observation of genetically divergent clades associated with mesophotic depths highlights that there are many more mesophotic-specialist coral species than currently acknowledged, and that an urgent assessment of this largely unstudied biological diversity is warranted.

evolutionary biology↗

Mesophotic gorgonian corals evolve multiple times and faster than deep and shallow lineages

1.Mesophotic Coral Ecosystems (MCEs) develop on a unique environment, where abrupt environmental changes take place. Using a time-calibrated molecular phylogeny (mtDNA: mtMutS), we examined the lineage membership of mesophotic gorgonian corals (Octocorallia: Cnidaria) in comparison to shallow and deep-sea lineages of the wider Caribbean-Gulf of Mexico and the Tropical Eastern Pacific. Our results show mesophotic gorgonians originating multiple times from old deep-sea octocoral lineages, whereas shallow-water species comprise younger lineages. The mesophotic gorgonian fauna in the studied areas are related to their zooxanthellate shallow-water counterparts in only two clades (Gorgoniidae and Plexauridae), where the shallow-deep gradient could serve as a driver of diversification. Interestingly, mesophotic clades have diversified faster than either shallow or deep clades. One of this groups with fast diversification is the family Ellisellidae, a major component of the mesophotic gorgonian coral assemblage worldwide.

evolutionary biology↗

Modeling multifunctionality of genes with secondary gene co-expression networks in human brain provides novel disease insights

MotivationCo-expression networks are a powerful gene expression analysis method to study how genes co-express together in clusters with functional coherence that usually resemble specific cell type behaviour for the genes involved. They can be applied to bulk-tissue gene expression profiling and assign function, and usually cell type specificity, to a high percentage of the gene pool used to construct the network. One of the limitations of this method is that each gene is predicted to play a role in a specific set of coherent functions in a single cell type (i.e. at most we get a single for each gene). We present here GMSCA (Gene Multifunctionality Secondary Co-expression Analysis), a software tool that exploits the co-expression paradigm to increase the number of functions and cell types ascribed to a gene in bulk-tissue co-expression networks. ResultsWe applied GMSCA to 27 co-expression networks derived from bulk-tissue gene expression profiling of a variety of brain tissues. Neurons and glial cells (microglia, astrocytes and oligodendrocytes) were considered the main cell types. Applying this approach, we increase the overall number of predicted triplets by 46.73%. Moreover, GMSCA predicts that the SNCA gene, traditionally associated to work mainly in neurons, also plays a relevant function in oligodendrocytes. AvailabilityThe tool is available at GitHub,https://github.com/drlaguna/GMSCA as open source software. ImplementationGSMCA is implemented in R.

bioinformatics↗

Endozoochory by parrotfish replenishes reefs with coral-associated microbiome

Sparisoma viride is the most abundant parrotfish in the Caribbean and is considered as the most important excavator due to corallivore behaviour. Parrotfishes are a keystone group that favour the growth and resilience of coral reefs removing macroalgae and structuring the benthic communities. The microbial symbiotic communities are involved in multiple functions related to nutrition and immunity maintaining corals health. Because S. viride scrape coral tissues, the skeleton and the algae on coral, it could be important reservoirs or vectors of microorganism for the corals through the faeces dispersion, however, the role of parrotfishes as reservoirs are poorly studied. Establishing microbial communities present in parrotfish faeces will contribute to understand the ecological impact of parrotfishes in coral resilience. We investigated the composition of disseminated bacteria and the extent to which the cell integrity of dinoflagellate photosymbionts (Symbiodiniaceae) is maintained in the faeces and compare with sediments and water column controls. Then, we analysed diversity and structure of bacterial communities at family level and search similarities between faeces of the study and coral associated microbiome reported in the literature. Similar levels of structural integrity and photosynthetic health of Symbidiodinaceae cells were found in both faeces and reef sediments. Besides, the sediments microbiome echoes the parrotfish faecal microbiome by sharing high diversity and a similar bacterial community composition. Several bacterial families were present in parrotfish faeces and in coral microbiome reported in the literature highlighting the dispersal potential of parrotfishes replenishing coral reefs. Despite the sampling limitations, these findings uncover the potential role of the excavator parrotfish in enriching environmental reservoirs, especially reef sediments, with coral-associated bacteria and photosynthetic microalgae. Parrotfishes could reinforce the coral microbiome and facilitate coral symbiont acquisition, key features critical to maintaining the fitness of one of the most threatened ecosystems on Earth. This finding could be considered as a first step in uncovering a mechanism for reef-microbiome maintenance.

ecology↗

Eiger/TNFα-mediated Dilp8 and ROS production coordinate intra-organ growth in Drosophila

Coordinated intra- and inter-organ growth is essential during animal development to generate individuals of proper size and shape. The Drosophila wing has been a valuable model system to reveal the existence of a stress response mechanism mediated by Drosophila p53 (Dmp53) and involved in the coordination of tissue growth between adjacent cell populations upon targeted reduction of growth rates. Here we present evidence that a two-step molecular mechanism is being used by Dmp53 to reduce in a non-autonomous manner growth and proliferation in adjacent cell populations. First, Dmp53-mediated transcriptional induction of Drosophila TNF ligand Eiger leads to cell autonomous activation of JNK. Second, two different signaling events downstream of the Eiger/JNK axis are induced in the growth depleted territory in order to independently regulate tissue size and cell number in adjacent cell populations. Whereas expression of the systemic hormone dILP8 coordinates intra-organ growth and final tissue size, induction of Reactive Oxygen Species downstream of Eiger/JNK and, as a consequence of apoptosis induction, acts non-cell-autonomously to regulate proliferation rates of adjacent epithelial cells. Our results unravel how local and systemic signals can act concertedly to coordinate growth and proliferation within an organ in order to generate well-proportioned organs and functionally integrated adults.\n\nAuthor SummaryCoordination of growth between the different parts of a given developing organ is an absolute requirement for the generation of functionally integrated structures during animal development. Although this question has fascinated biologists for centuries, the responsible molecular mechanisms have remained so far unknown. In this work, we have used the developing wing primordium of Drosophila to identify the molecular mechanisms and signaling molecules mediating communication between adjacent cell populations upon targeted reduction in growth rates. We first present evidence that activation of Drosophila p53 in the growth-depleted territory induces expression of the fly TNF ligand Eiger which cell autonomously activates the JNK stress signaling pathway. While JNK-dependent expression of the systemic hormone dILP8 reduces growth and final size of the adjacent territories, production of Reactive Oxygen Species downstream of JNK and the apoptotic machinery act locally to regulate proliferation rates in adjacent epithelial cells. Our data reveal how signals acting locally or systemically can regulate cell proliferation and growth independently to accomplish coordination in tissue size and cell number among different parts of an organ in order to give rise to well-proportioned adult structures.\n\nHIGHLIGHTS{checkmark} Dmp53-dependent Eiger expression is required to coordinate intra-organ growth\n{checkmark}Eiger acts through its receptor Grindelwald and JNK signaling to reduce growth and proliferation rates in a non-cell-autonomous manner\n{checkmark}Eiger/JNK-dependent Dilp8 expression coordinates intra-organ growth but not proliferation\n{checkmark}Eiger/JNK activation triggers ROS production\n{checkmark}ROS act non-cell-autonomously to regulate proliferation of adjacent epithelial cells.

developmental biology↗