Biology subjects

Pereira Lobo, F.

Publications and source records attributed to Pereira Lobo, F..

5 recordsLinked to original sources

bioRxiv2026

BSG.S regulates ionocyte radial intercalation and function in the developing Xenopus mucociliary epithelium.

Mucociliary epithelia (MCE) line multiple vertebrate organs, including the mammalian airways, and rely on coordinated interactions among specialized cell types to clear pathogens and maintain epithelial homeostasis. Proper MCE function requires the appropriate specification and spatial organization of ionocytes, multiciliated cells, secretory cells, and basal cells. Ionocytes regulate ion transport and pH homeostasis, yet the mechanisms governing their integration and function within the developing epithelium remain incompletely understood. Basigin (BSG), also known as CD147 or EMMPRIN, is a conserved transmembrane glycoprotein implicated in cell migration, adhesion, and signaling. However, its role in mucociliary epithelial development remains unclear. Here, we show that the short isoform of BSG (BSG.S) is expressed in ionocytes of the Xenopus laevis MCE. Our findings demonstrate that BSG.S depletion impairs ionocyte radial intercalation, alters intracellular pH, and disrupts epithelial organization. Furthermore, BSG.S loss alters epithelial cell-type composition, decreasing the number of basal cells and increasing the number of multiciliated cells. These findings suggest BSG.S as a regulator of ionocyte integration, epithelial organization, and cell-type composition during mucociliary epithelial development.

developmental biology↗

bioRxiv2026

Common germline polymorphisms and somatic cancer mutations exhibit non-random positional overlap across the human genome

Germline and somatic mutations have traditionally been studied independently because they arise in distinct biological contexts and are shaped by different selective pressures. Despite these differences, both originate from the same molecular processes of DNA damage, replication error, and DNA repair. Yet this separation has limited the opportunity of investigation of genomic loci recurrently mutated across both mutational landscapes. Identifying such mutational co-occurrences may provide unique insights into the principles governing recurrent mutation. Here, we show that common germline polymorphisms and cancer-associated somatic SNVs recur at identical genomic positions across the human genome, sharing the same nucleotide substitutions more frequently than expected by chance. This recurrence persists within coding regions, is only minimally explained by the canonical hotspot contexts evaluated here (CpG islands and microsatellites), and is associated with a mutational signature profile enriched for the ubiquitous clock-like SBS5 signature together with DNA repair-associated signatures. Importantly, this overlap pattern is not shared across other germline variation: rare (AF<1%) and clinically classified variants exhibit significantly less overlap than expected. Together, these findings support the existence of intrinsically vulnerable genomic loci and provide a framework for investigating the mechanisms underlying recurrent mutation.

bioinformatics↗

bioRxiv2025

Sp Transcription Factors Establish the Signaling Environment in the Neuromesodermal Progenitor Niche During Axial Elongation

Neuromesodermal competent progenitors (NMCs) are located in the caudal epiblast near the node and primitive streak and give rise to spinal cord and somitic mesoderm during trunk and tail elongation. Their self-renewal depends on an autoregulatory loop involving Wnt3a and Fgf signaling, and the Tbxt and Cdx transcription factors, but the mechanisms underlying loop formation and the establishment of the niche are poorly understood. Here, we identify the zinc-finger transcription factors Sp5 and Sp8 (Sp5/8) as essential regulators of NMC maintenance. Sp5/8 expression is controlled by Wnt, Fgf and retinoic acid signaling, and they cooperate with Tbxt, Tcf7 and Cdx2 to sustain a robust autoregulatory network that promotes high Wnt/Fgf and low retinoic acid activity in the niche. These factors bind a novel enhancer essential for Wnt3a expression and feedback-loop integrity. Mechanistically, Sp5/8 regulate the dynamic exchange of activating and repressive Tcf complexes at Wnt-responsive enhancers. Our findings define a transcriptional module centered on Sp5/8 that stabilizes niche signaling and transcriptional circuitry essential for NMC fate decisions and trunk development.

developmental biology↗

bioRxiv2024

Phylogeny-aware modeling uncovers molecular functional convergences associated with complex multicellularity in Eukarya

A major trait of Eukarya is the independent evolution of complex multicellular lineages of animals and plants with specialized cell types organized in tissues, organs and systems. The number of cell types (NCT) has been commonly adopted as a proxy in comparative studies investigating the genomic evolution of biological complexity. Although expansions of homologous genes playing roles in extracellular processes, signal transduction pathways, and the immune system have been reported as associated with NCT variation in metazoans, the evolutionary patterns coordinating the genomic evolution of multicellularity throughout Eukarya remain poorly understood. We used Gene Ontology (GO) as a genome annotation scaffold to represent biological functions shared by genes regardless of their homology relationships to search for molecular functional convergences associated with NCT. For that we integrated phenotypic, genomic, annotation and phylogenetic data to build phylogeny-aware models and searched for expansions of homologous regions and of GO terms associated with NCT values across 49 eukaryotic species, including complex multicellular plants and metazoans. Virtually all homologous regions associated with NCT are metazoan- and vertebrate-specific expansions of paralogs with key roles in developmental pathways. The functional annotation, in contrast, detected previously unknown biological themes coded by non-homologous genes independently expanded in multicellular plants and metazoans, such as system and anatomical development, immunity, regulatory mechanisms of embryogenesis, response to external stimuli and detection of natural rhythmic processes. Our findings unveil functional molecular convergences shared by these contrasting groups due to common selective pressures in the lifestyle of complex multicellular lineages.

evolutionary biology↗

bioRxiv2021

CALANGO: an annotation-based, phylogeny-aware comparative genomics framework for exploring and interpreting complex genotypes and phenotypes

The increasing availability of genomic, annotation, evolutionary and phenotypic data for species contrasts with the lack of studies that adequately integrate these heterogeneous data sources to produce biologically meaningful knowledge. Here, we present CALANGO, a phylogeny-aware comparative genomics tool that uncovers functional molecular convergences and homologous regions associated with quantitative genotypes and phenotypes across species, enabling the fast discovery of novel statistically sound, biologically relevant phenotype-genotype associations. We demonstrate the usefulness of CALANGO in two case studies. The first one unveils potential causal links between prophage density and the pathogenicity phenotype in Escherichia coli, and confidently demonstrates how CALANGO supports the investigation of basic causal relationships by enabling a level of counterfactual investigation of observed associations in the data. As a second case study, we used our tool to search for homologous regions associated with a complex phenotypic trait in a major group of eukaryotes: the evolution of maximum height in angiosperms. We confidently identify a previously unknown association between maximum plant height and the expansion of the self-incompatibility system, a molecular mechanism that prevents inbreeding and increases genetic diversity. Taller species also have lower rates of molecular evolution due to their longer generation times, a critical concern for their long-term viability. The new mechanism we report could counterbalance this fact, and have far-reaching consequences for fields as diverse as conservation biology and agriculture. CALANGO is provided as a fully operational R package that can be freely installed from CRAN.

bioinformatics↗