Biology subjects

Cruz, J.

Publications and source records attributed to Cruz, J..

18 recordsLinked to original sources

bioRxiv2026

CRISPR RNA-Guided Integrase Enables Targeted Genome Engineering and Prophage Functional Genomics in Plant-Pathogenic Pseudomonas

Pseudomonas species include important plant pathogens responsible for substantial agricultural losses. Although CRISPR-INTEGRATE has been applied for genome engineering in medically relevant Pseudomonas, its utility in plant-pathogenic Pseudomonas has not been established. Here, we demonstrate CRISPR-INTEGRATE, an RNA-guided Tn7-like transposition system that enables targeted chromosomal integration without double-strand breaks or host-dependent homologous recombination, across three plant-pathogenic Pseudomonas backgrounds. Targeted disruption of hrpJ, hrcC, and gacA was confirmed by PCR and Sanger sequencing and resulted in distinct phenotypes, including impaired type III secretion-associated virulence and hypersensitive response, altered colony morphology and biofilm formation, and reduced motility. We further coupled CRISPR-INTEGRATE with Cre-lox recombination to excise a ~40-kb prophage-associated region from the P. syringae pv. tomato DC3000 chromosome. Genomic characterization identified a 33.45-kb predicted prophage within this region, putative attL/attR sites sharing an identical 14-bp core sequence, an orthologous empty locus containing a candidate attB site, and conserved prophage-associated gene organization across P. syringae genomes. Deletion of the region altered bacterial growth and increased susceptibility to phage infection, with the strongest effect observed for phage Plaza, while having no detectable effect on the tested plant virulence phenotypes. Together, these findings establish CRISPR-INTEGRATE as a portable genome-engineering platform for plant-pathogenic Pseudomonas and demonstrate its utility for functional interrogation of individual genes and large accessory genomic elements.

pathology↗

bioRxiv2026

Evolutionary landscapes of zygotic genome activation across animals

During early animal embryogenesis, gene expression control shifts from maternally deposited products to newly transcribed RNA through zygotic genome activation (ZGA). Although essential and universal, ZGA remains poorly understood outside a few model species. Here, we generated a transcriptomic atlas of early embryogenesis across 61 animal species from 13 phyla and used a unified computational framework to infer ZGA timing systematically. We find extensive variation in ZGA onset across animals, but show that the ratio between genome size and egg cytoplasmic volume, a proxy for the nuclear-to-cytoplasmic ratio, robustly predicts when genome activation begins. We also reveal that zygotic genes also differ from maternal transcripts in genomic architecture, function and evolutionary conservation, suggesting that ZGA follows a conserved molecular logic despite flexible transcriptomic outputs.

evolutionary biology↗

bioRxiv2025

Sheathless elasto-inertial focusing of sub-25 nm particles in straight microchannels

Nanoscale biological particles, such as lipoproteins (10-80 nm) or extracellular vesicles (30-200 nm), play pivotal roles in health and disease, including conditions like cardiovascular disorders and cancer. Their effective analysis is crucial for applications in diagnostics, quality control, and nanomedicine development. While elasto-inertial focusing offers a powerful method to manipulate particles without external fields, achieving consistent focusing of nanoparticles (<500 nm) has remained a challenge. In this study, we experimentally demonstrate elasto-inertial focusing of nanoparticles as small as 25 nm using straight high-aspect-ratio microchannels in a sheathless flow. Systematic investigations reveal the influence of channel width, particle size, viscoelastic concentration, and flow rate on focusing behavior. Additionally, through numerical simulations and experimental validation, we provide insights into particle migration dynamics and viscoelastic forces governing nanoparticle focusing. Finally, we successfully focus biological particles, including liposomes (90-140 nm), extracellular vesicles (100 nm), and lipoproteins (10-25 nm), under optimized conditions, showcasing potential applications in medical diagnostics and targeted drug delivery. These findings mark a significant advancement toward size-based high-resolution particle separation, with implications for biomedicine and environmental sciences.

bioengineering↗

bioRxiv2024

Single cell transcriptomics of X-ray irradiated Drosophila wing discs reveals heterogeneity related to cell-cycle status and cell location

Even seemingly homogeneous populations of cells can express phenotypic diversity in response to environmental changes. Thus, X-ray irradiation of tissues composed of diverse cell types can have complex outcomes. We have used single-cell RNA-sequencing to study the effects of X-ray radiation on the Drosophila wing imaginal disc, a relatively simple tissue composed mostly of epithelial cells. Transcriptomic clustering of cells collected from the wing disc generates clusters that are mainly grouped based on proximodistal cell location. To quantify heterogeneity of gene expression among clusters, we adapted a metric used to study market concentration, the Herfindahl-Hirschman Index. Genes involved in DNA damage repair, defense against reactive oxygen species, cell cycle progression, and apoptosis are expressed relatively uniformly. In contrast, genes encoding a subset of ligands, notably cytokines that activate the JAK/STAT pathway, some transcription factors including Ets21C, previously implicated in regeneration, and several signaling proteins are expressed more regionally. Though the radiation-responsive transcription factor p53 is expressed relatively uniformly in the wing disc, several regionally-induced genes still require p53 function, indicating that regional and radiation-induced factors combine to regulate their expression. We also examined heterogeneity within regions using a clustering approach based on cell cycle gene expression. A subpopulation of cells, characterized by high levels of tribbles expression, is amplified in irradiated discs. Remarkably, this subpopulation accounts for a considerable fraction of radiation-induced gene expression, indicating that cellular responses are non-uniform even within regions. Thus, both inter-regional and intra-regional heterogeneity are important features of tissue responses to X-ray radiation.

genomics↗

bioRxiv2024

From Quantitative Trait Loci towards Mechanisms: Linkage Integration Hypothesis Testing (LIgHT) Sheds Light on the Mechanisms of Genetically Modulated Stress Tolerance

The goal of this work is to assess the mechanistic bases of natural genetic variations in plant responses of photosynthesis to stress. To achieve this goal, we devised the Linkage Integration Hypothesis Testing (LIgHT) approach, comparing chromosomal locations of quantitative trait loci (QTL) for multiple phenotypes to distinguish between hypothetical mechanisms. As a use case, we explored genetic variations in photosynthesis-related processes under chilling stress in recombinant inbred lines of cowpea (Vigna unguiculata L. Walp.). We focused on photosynthesis-related parameters measurable in high throughput and indicative of proposed chilling responses, including the states of photosystems I (PSI) and II (PSII), photoprotective nonphotochemical quenching, PSII photodamage, and nyctinastic leaf movements (NLM). The patterns of QTL linkages indicated chilling stress tolerance is genetically controlled by avoiding PSII photodamage rather than PSI damage or NLM. This model was validated in a separate experiment measuring the rates of PSII photodamage and repair. Additional linkages suggest that chilling-induced damage to PSII is controlled by the thylakoid proton motive force and redox state of PSII. This regulation is modulated by thylakoid fatty acid composition, as suggested in Hoh et al., 2022. We propose the LIgHT approach can be broadly applied to test mechanisms underlying genetic variations. HighlightThis work Introduces the Linkage Integration Hypothesis Testing (LIgHT) approach for mechanistic studies of natural variations, identifying photosynthetic regulatory mechanisms underlying natural variations to abiotic stresses by applying this approach.

plant biology↗

bioRxiv2024

E93 controls adult differentiation by repressing broad in Drosophila

In Drosophila melanogaster, successful development relies on the precise coordination of both spatial and temporal regulatory axes. The temporal axis governs stage-specific identity and developmental transitions through a number of genes, collectively forming the Metamorphic Gene Network. Among these, Ecdysone inducible protein 93F (E93) serves as the critical determinant for adult specification, but its mechanism of action remains unclear. Here, we found that, rather than acting as an instructive signal, E93 promotes adult differentiation through the repression of the pupal specifier broad (br). In the absence of E93, sustained high levels of Br during the pupal stage strongly represses pupal-specific enhancers that are essential for the terminal differentiation of the wing. We also show that Br represses the pupal-enhancers during the larval and prepupal stages preventing the premature implementation of the adult genetic program, and that it also dampens the activity of larval enhancers during the latter stages of larval development. This mechanism of action seems to be a derived feature acquired in Diptera, as in the coleopteran Tribolium castaneum, repression of br by E93 is not sufficient to allow adult differentiation. In summary, our study elucidates the crucial role of the intricate interplay between E93 and Br as the governing mechanism in the process of terminal differentiation in Drosophila. This discovery holds significant implications for advancing our understanding of the evolution of insect metamorphosis.

developmental biology↗

bioRxiv2023

Spatial behaviors and seasonal habitat use of an increasingly endangered Neotropical psittacine, the thick-billed parrot (Rhynchopsitta pachyrhyncha)

The thick-billed parrot (Rhynchopsitta pachyrhyncha) inhabits highland pine forests in the Sierra Madre Occidental ranges of northwestern Mexico. Their populations have declined significantly to <2000 individuals due to habitat loss, illegal hunting and increasing predation. Despite their ecological and cultural importance and increasingly endangered status, the species is data deficient. Our study aimed to inform and enhance conservation management strategies for thick-billed parrots with information on their spatial ecology, habitat use, migratory behaviors and social associations. We deployed biotelemetry devices to conduct the first tracking study of wild thick-billed parrots. Our study revealed that thick-billed parrots are seasonal migrators, departing their breeding habitats around October and returning from southern habitats around April. Our research also identified previously unknown overwintering sites and migratory stopover locations, as well as a new nesting site. The parrots exhibited high spatial variability in range shifting behavior, but all tracked parrots exhibited range shifts during migration, with durations of 3 to 181 days and distances of 173 to 765 km. They traveled in close social groups and migratory routes primarily followed high-elevation forests along the Sierra Madre Occidental ranges. Home range analysis indicated smaller breeding site ranges and larger overwintering ranges, possibly reflecting nesting constraints and winter food resource dispersion. Parrot spatial associations favored high-elevation forest landscapes with tall and wide-trunked trees, underscoring the importance of preserving old-growth forests for nesting and foraging. Less than 20 % of parrot habitats have formal regulatory protections. Conservation management efforts must focus on increasing protections for nesting areas, overwintering habitats, and key migratory stopover sites. As climate change exacerbates regional threats, integrated management plans involving local stakeholders and communities are essential for the parrots long-term survival and the preservation of their old-growth forest habitats.

ecology↗

bioRxiv2023

Artificial intelligence-driven morphology-based enrichment of malignant cells from body fluid

Cell morphology is a fundamental feature used to evaluate patient specimens in pathological analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with high background of non-malignant cells, restricting the ability for downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multi-dimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low-levels or undetectable in pre-sort patient samples. Combined, our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multi-dimensional morphology analysis, and microfluidic sorting.

pathology↗

bioRxiv2022

Pervasive evolution of tissue-specificity of ancestral genes differentially shaped vertebrates and insects

Regulation of gene expression is arguably the main mechanism contributing to tissue phenotypic diversity within and between species. Here, we assembled an extensive transcriptomic dataset covering twenty bilaterian species and eight tissues, selecting a specular phylogeny that allowed both the combined and parallel investigation of gene expression evolution between vertebrates and insects. We specifically focused on widely conserved ancestral genes, identifying strong cores of pan-bilaterian tissue-specific genes and even larger groups that diverged to define vertebrate and insect tissues. Systematic inferences of tissue-specificity gains and losses show that nearly half of all ancestral genes have been recruited into tissue-specific transcriptomes. This occurred during both ancient and, especially, recent bilaterian evolution, with several gains being associated with the emergence of unique phenotypes. Such pervasive evolution of tissue-specificity was linked to gene duplication coupled with specialization, including an unappreciated prolonged effect of whole genome duplications during recent vertebrate evolution.

genomics↗

bioRxiv2022

Buforin II-Escherichia coli's DNA interactome: Detailed biophysical characterization revealed nanoscale complexes likely formed by DNA supercoiling

Antimicrobial peptides (AMPs) have emerged as exciting alternatives to the alarming increase of multiresistant bacteria due to their high activity against them through mechanisms that are thought to largely avoid resistance in the long term. Buforin II (BUFII) is an antibacterial peptide hypothesized to kill bacteria by crossing their membranes to interact with intracellular molecules and interrupt key processes for survival. In particular, interactions with DNA have been considered crucial for triggering cell death mechanisms. However, such interactions are still unknown, and thus far, no reports are available describing BUFII-DNA complexes. Here, we describe a complete biophysical study of the interaction between BUFII and Escherichia coli gDNA via spectrofluorimetric, spectroscopic, and microscopic techniques, complemented with whole-genome sequencing. The E. colis DNA-BUFII interactome was isolated by an in vitro pull-down method aided by BUFII-magnetite nanobioconjugates. Our results demonstrated that DNA-BUFII formed round-shape nanoscale complexes by strong electrostatic interactions, likely occurring nonspecifically throughout the entire bacterial genome. Further sequencing of the isolated DNA fragments corroborated this notion and led to hypothesize that BUFII is possibly responsible for inducing DNAs supercoiling. Other evidence for this idea was provided by the significant DNA conformational changes observed upon interaction with BUFII. Even though the evidence found fails to describe the complete action mechanism of BUFII in vivo, our findings pave the way to engineer DNA-peptide supramolecular complexes very precisely, which might find application in the field of gene therapy delivery.

biophysics↗

bioRxiv2022

Ecdysone signaling controls early embryogenesis in the short-germ hemimetabolous insect Blattella germanica.

Steroid hormone signaling is a central regulator of insect development especially during the post-embryonic period. However, its role during embryonic development is less understood, particularly in short-germ band hemimetabolous insects. Here, we used the short-germ band hemimetabolous insect Blattella germanica to analyse the functions of 20-hydroxyecdysone (20E), the most active insect steroid, signaling during the embryonic stage. We show that the heterodimeric 20E receptor, BgEcR-A and BgRXR, is present from the beginning of embryogenesis and that a stereotypical 20E-dependent cascade of nuclear receptors is first detected at the early blastoderm stage. Using parental RNAi, we show that both receptors are required for the proper formation of the germ band by controlling cell proliferation during the blastoderm stage. In addition, they are also required for the coordinated induction of the 20E-induced cascade of nuclear receptors. Finally, we show that two of these nuclear receptors, BgHR3 and BgFTZ-F1, have relevant roles in germ band formation. Whereas BgHR3 controls the formation and development of the cephalic region of the germ band, BgFTZ-F1 stripped expression suggested a role in the segmentation of the germ band. In summary, our results show that 20E-signaling is required much earlier in short-germ band hemimetabolous than in long-germ band holometabolous embryogenesis, which raises the possibility that the loss of 20E-signaling during the initial stages of embryogenesis could be a key feature in the evolution of the different types of insect development.

developmental biology↗

bioRxiv2022

Realtime morphological characterization and sorting of unlabeled viable cells using deep learning

Phenotyping of single cells has dramatically lagged advances in molecular characterization and remains a manual, subjective, and destructive process. We introduce COSMOS, a platform for phenotyping and enrichment of cells based on deep learning interpretation of high-content morphology data in realtime. By training models on an atlas of >1.5 billion images, we demonstrate enrichment of unlabeled cells up to 33,000 fold. We apply COSMOS to multicellular tissue biopsy samples demonstrating that it can identify malignant cells with similar accuracy to molecular approaches while enriching viable cells for functional evaluation. We show high-dimensional embedding vectors of morphology generated by COSMOS without any need for complex sample pre-processing, gating, or bioinformatics capabilities, which enables discovery of cellular phenotypes, and integration of morphology into multi-dimensional analyses. One sentence summaryA novel platform capable of high-throughput imaging and gently sorting cells using deep morphological assessment.

cell biology↗

bioRxiv2022

Broadly-recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles

Sequence homology between SARS-CoV-2 and common-cold human coronaviruses (HCoVs) raises the possibility that memory responses to prior HCoV infection can impact the T cell response in COVID-19. We studied T cells recognizing SARS-CoV-2 and HCoVs in convalescent COVID-19 donors, and identified a highly conserved SARS-CoV-2 sequence S811-831, with two overlapping epitopes presented by common MHC-II proteins HLA-DQ5 and HLA-DP4. These epitopes were recognized by CD4+ T cells from convalescent COVID-19 donors, mRNA vaccine recipients, and by low-abundance CD4+ T cells in uninfected donors. TCR sequencing revealed a diverse repertoire with public TCRs. CD4+ T cell cross-reactivity was driven by the remarkably strong conservation of T cell contact residues in both HLA-DQ5 and HLA-DP4 binding frames, with distinct patterns of HCoV cross-reactivity explained by MHC-II binding preferences and substitutions at secondary TCR contact sites. These data highlight S811-831 as a highly-conserved CD4+ T cell epitope broadly recognized across human populations.

immunology↗

bioRxiv2022

Cell culture model system utilizing engineered A549 cells to express high levels of ACE2 and TMPRSS2 for investigating SARS-CoV-2 infection and antivirals

Novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an imminent global threat since its initial outbreak in December 2019. A simple in vitro model system using cell lines highly susceptible to SARS-CoV-2 infection are critical to facilitate the study of the virus cycle and to discover effective antivirals against the virus. Human lung alveolar A549 cells are regarded as a useful and valuable model for respiratory virus infection. However, SARS-CoV-2 uses the ACE2 as receptor for viral entry and the TMPRSS2 to prime the Spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a robust human lung epithelial cell-based model by transducing ACE2 and TMPRSS2 into A549 cells and show that the ACE2 enriched A549ACE2/TMPRSS2 cells (ACE2plus) and its single-cell-derived subclone (ACE2plusC3) are highly susceptible to SARS-CoV-2 infection. These engineered ACE2plus showed higher ACE2 and TMPRSS2 mRNA expression levels than currently used Calu3 and commercial A549ACE2/TMPRSS2 cells. ACE2 and TMPRSS2 proteins were also highly and ubiquitously expressed in ACE2plusC3 cells. Additionally, antiviral drugs like Camostat mesylate, EIDD-1931, and Remdesivir strongly inhibited SARS-CoV-2 replication. Notably, multinucleated syncytia, a clinical feature commonly observed in severe COVID-19 patients was induced in ACE2plusC3 cells either by virus infection or by overexpressing the Spike proteins of different variants of SARS-CoV-2. Syncytial process was effectively blocked by the furin protease inhibitor, Decanoyl-RVKR-CMK. Taken together, we have developed a robust human A549 lung epithelial cell-based model that can be applied to probe SARS-CoV-2 replication and to facilitate the discovery of SARS-CoV-2 inhibitors.

cell biology↗

bioRxiv2021

Expression and novel alternative purification of the recombinant nucleocapsid (N) protein of SARS-CoV-2 in Escherichia coli for the serodiagnosis of COVID-19

The SARS-CoV-2 coronavirus causes severe acute respiratory syndrome and has caused a global pandemic by causing the COVID-19 disease. To monitor and control it, diagnostic methods such as molecular and serological tests are necessary. The serological approach uses SARS-CoV-2 antigens to detect the antibodies present in patients using quantitative techniques such as enzyme-linked immunosorbent assay (ELISA) or qualitative rapid tests such as lateral flow chromatography (RDTs). The main antigens used are the spike protein (S) and the nucleocapsid protein (N). Both proteins are obtained in different expression systems, in eukaryotic cells, their production is expensive, so in this work we chose a simpler and cheaper system such as prokaryotic to express and purify the N protein. Thereore, the nucleotide sequence had to being optimized to be expressed in Escherichia coli. The protein N is sensitive to E.coli proteases and also has the ability to self-proteolyze under native conditions, degrading into different fragments. However, under denaturing conditions, using urea and at pH 5.3 it is stable and efficiently purified using metal exchange chromatography (IMAC). In our purification strategy, we surprisingly found that by not using a sonicator, a homogeneous and time-stable preparation of the recombinant antigen is obtained. An approximate yield of 200 mg / L was obtained. It was then tested with healthy sera and sera from COVID-19 convalescent patients in Wester-blot tests that were able to recognize it. Our work provides a novel strategy to produce the SARS-CoV-2 protein N so that it can be used as an input in the development and innovation of serological tests in the diagnosis of COVID-19.

cell biology↗

bioRxiv2021

Recombinant haplotypes reflect sexual reproduction in symbiotic arbuscular mycorrhizal fungi

Arbuscular mycorrhizal fungi (AMF) are part of the most widespread fungal-plant symbiosis. They colonize at least 80% of plant species, promote plant growth and plant diversity. These fungi are multinucleated and contain either one or two haploid nuclear genotypes (monokaryon and dikaryon) identified by the alleles at a putative mating-type locus. This taxon has been considered as an ancient asexual scandal because of the lack of observable sexual structures. Despite identification of a putative mating-type locus and functional activation of genes related to mating when two isolates co-exist, it remains unknown if AMF take part in a mainly sexual life cycle. We used publicly available genome sequences to test if dikaryon genomes display signatures of sexual reproduction in the form of reciprocal recombination patterns, or if they display signatures of parasexual reproduction involving gene conversion. We used short-read and long-read sequence data to identify nucleus genotype-specific haplotypes within dikaryons and then compared them to orthologous gene sequences from related monokaryon isolates displaying the same putative MAT-types. We observed that these genotype-specific haplotypes display reciprocal recombination and not gene conversion. These results are consistent with a sexual origin of the dikaryon rather than a parasexual origin and provides an important step to understand the life cycle of these globally important symbiotic fungi.

evolutionary biology↗

bioRxiv2018

DETECTION AND MOLECULAR EPIDEMIOLOGY OF HUMAN BOCAVIRUS IN CHILDREN WITH ACUTE GASTROENTERITIS FROM BRAZIL

Human Bocavirus (HBoV) is a recently discovered virus and was first detected in the nasopharyngeal aspirate samples and after in stool samples, suggesting that HBoV may be a causative agent for human enteric infections. Due to absence of treatment options, there is a need to understand the disease-causing mechanism of these viruses. The aim of this was to demonstrate the prevalence of HBoV from children less than 10 years with acute gastroenteritis in Brazil, during November 2011 to November 2012. Stool samples from hospitalized children [≤] 10 years who presented symptoms of acute gastroenteritis were analyzed for the presence of HBoV DNA by nested-PCR. HBoV- positivity was detected in 24.0% (54/225) of samples. Two peaks of HBoV detection were observed, during November 2011 and July to September 2012. Co-infections between HBoV and rotavirus A were identified in 50.0% (27/54) of specimens. Phylogenetic analysis identified the presence of HBoV-1 (94.8%), HBoV-2 (2.6%) and HBoV-3 (2.6%) species, with only minor variations among them. Further investigations are necessary to improve the knowledge on the role of HBoV in gastrointestinal infections.

microbiology↗

bioRxiv2018

Dual role of Bnl/Fgf signaling in proliferation and endoreplication of Drosophila trachealadult progenitor cells

AbstractAdult progenitor cells activation is a key event in the formation of adult organs during development. The initiation of proliferation of these progenitor cells requires specific temporal signals, mostly of them still unknown. In Drosophila, formation of adult tracheal system depends on the activation of tracheal adult progenitors (tracheoblasts) of Tr4 and Tr5 tracheal metamers specific spiracular branches (SB) during the last larval stage. The mitotic activity of these tracheoblasts generate a pool of tracheal differentiated cells that migrate during pupal development along the larval trachea by the activation of the Branchless (Bnl)/Fibroblast growth factor (FGF) signaling to form the abdominal adult tracheal system. In here, we found that, in addition to migration, Bnl/FGF signaling, mediated by the transcription factor Pointed, is also required for adult progenitor cell proliferation in the SBs. Moreover, we found that tracheoblast proliferation in Tr4 and Tr5 SBs relies on the specific expression of the FGF ligand Bnl in their nearby transverse connective branches. Finally, we also show that, in absence of the transcription factor Cut (Ct), Bnl/FGF signaling induces endoreplication of differentiated tracheoblast daughter cells by in part promoting Fizzy-related (Fzr) expression. Altogether, our results suggest a dual role of Bnl/FGF signaling in tracheal adult progenitors, inducing both proliferation and endoreplication of tracheoblasts in late larval development, depending on the presence or absence of the transcription factor ct, respectively.\n\nAuthor summaryThe generation of adult organs and tissue renewal are complex processes that depend on the proliferation and posterior differentiation of undifferentiated progenitor cells in a temporal coordinated manner. Although many signals that regulate the activity of progenitor cells have been identified, the characterization of the mechanisms underlying the temporal and spatial control of such events remain unknown. The tracheal system of Drosophila, the respiratory organ, forms during embryogenesis and it is remodeled during metamorphosis from quiescent adult progenitor cells that proliferate. We have discovered that this proliferation depends on the activation of the FGF signaling as mutations that either inactivate or over-activate the pathway blocks cell division or induced over-proliferation of progenitor cells, respectively. Interestingly, we have found that the same signaling pathway also controls tracheal progenitor cells differentiation by promoting endoreplication. We found that this dual role of FGF signaling in adult progenitor cells, depends on the presence or absence of the transcription factor Cut. Altogether, our results, reveal the mechanism that control the division and differentiation of progenitor cells and open the possibility that analogous signaling pathway may play a similar role in vertebrate stem cell regulation and tumor growth.

developmental biology↗