A bHLH interaction code controls bipotential differentiation and self-renewal in the Drosophila gut

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115398 - 115398

Published: March 1, 2025

Multipotent adult stem cells balance self-renewal with differentiation into various cell types. How this is regulated at the transcriptional level poorly understood. Here, we show that a network of basic helix-loop-helix (bHLH) transcription factors controls both stemness and bipotential in Drosophila intestine. We find homodimers Daughterless (Da), homolog mammalian E proteins, maintain intestinal (ISCs), antagonizing enteroendocrine fate promoted by heterodimers Da Scute (Sc; ASCL). The HLH factor Extramacrochaetae (Emc; homologous to Id proteins) promotes absorptive titrating Sc. Emc prevents committed progenitor from dedifferentiating, underscoring plasticity these cells. Switching physical interaction partners way enables active maintenance while priming for along two alternative fates. Such regulatory logic likely operative other bipotent systems.

Language: Английский

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Ca2+ channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity

eLife, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 18, 2024

Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it thus critical to determine the factors contribute functional diversity synapses. We investigated contributions voltage-gated calcium channel (VGCC) abundance, spatial organization, subunit composition synapse among between synapses formed by two closely related Drosophila glutamatergic motor neurons with distinct neurotransmitter release probabilities (P r ). Surprisingly, VGCC levels are highly predictive heterogeneous P individual either low- or high-P inputs, but not inputs. find same number VGCCs more densely organized at synapses, consistent tighter VGCC-synaptic vesicle coupling. generated endogenously tagged lines investigate subunits vivo found α2δ–3 Straightjacket along CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators VGCCs, less abundant yet positively correlate input. Consistently, Bruchpilot dynamically increased across AZs inputs when potentiated maintain stable following glutamate receptor inhibition. Together, these findings suggest model which AZ abundance intersects input-specific molecular organization shape

Language: Английский

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OrthoDB and BUSCO update: annotation of orthologs with wider sampling of genomes

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(D1), P. D516 - D522

Published: Nov. 13, 2024

OrthoDB (https://www.orthodb.org) offers evolutionary and functional annotations of orthologous genes in the widest sampling eukaryotes, prokaryotes, viruses, extending experimental gene function knowledge to newly sequenced genomes. We collect annotations, delineate hierarchical orthology annotate groups (OGs) with traits. is leading resource for species diversity, striving sample most diverse well-researched organisms highest quality genomic data. This update expands include 5827 eukaryotic have also added coding DNA sequences (CDSs) loci coordinates. can be browsed, downloaded, or accessed using REST API, SPARQL/RDF now via API packages Python R Bioconductor. OrthoLoger (https://orthologer.ezlab.org), tool used inferring orthologs OrthoDB, available as a Conda package through BioContainers. ODB-mapper, component OrthoLoger, streamlines annotation from genomes descriptors. The benchmarking sets universal single-copy (BUSCO), derived had correspondingly major update. BUSCO (https://busco.ezlab.org) has become standard genomics, uniquely capable assessing both prokaryotic species. It applicable sets, transcriptomes, genome assemblies metagenomic bins.

Language: Английский

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An endogenous retroviral element co-opts an upstream regulatory sequence to achieve somatic expression and mobility

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Retrotransposons, multi-copy sequences that propagate via copy-and-paste mechanisms involving an RNA intermediate, occupy large portions of all eukaryotic genomes. A great majority their manifold copies remain silenced in somatic cells, nevertheless, some are transcribed, often a tissue specific manner, and small fraction retains its ability to mobilize. Retrotransposon expression or mobility increasingly recognized contribute normal development homeostasis, as well aging disease. While it is characterized retrotransposon may provide cis regulatory elements for neighboring genes, how own achieved different contexts not understood. Here, using long-read DNA sequencing, we characterize retrotransposition the Drosophila intestine. We show retroelement does change significantly upon limited very few active sub-families retrotransposons. Importantly, identify polymorphic donor locus endogenous LTR retroviral element rover , intestinal tissue. reveal gut activity copy depends on genomic environment. Without affecting local gene expression, co-opts upstream enhancer sequence, rich transcription factor binding sites, expression. Further escargot, snail-type critical progenitor cell function, can drive transcriptional copy. These data new insights into locus-specific features allow retrotransposons produce functional transcripts mobilize lineage.

Language: Английский

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Hypoxia-inducible factor 1α is required to establish the larval glycolytic program inDrosophila melanogaster

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

The rapid growth that occurs during Drosophila larval development requires a dramatic rewiring of central carbon metabolism to support biosynthesis. Larvae achieve this metabolic state, in part, by coordinately up-regulating the expression genes involved carbohydrate metabolism. resulting program exhibits hallmark characteristics aerobic glycolysis and establishes physiological state supports growth. To date, only factor known activate glycolytic is Estrogen-Related Receptor (dERR). However, dERR dynamically regulated onset switch, indicating other factors must be involved. Here we discover Sima, ortholog Hif1α, also essential for establishing program. Using multi-omics approach, demonstrate sima mutants fail properly die with defects phenocopy mutants. Moreover, Sima/Hif1α protein accumulation mutually dependent, as loss either transcription results decreased abundance protein. Considering mammalian homologs ERR Hif1α cooperatively regulate cancer cells, our findings establish fly powerful genetic model studying interaction between these two key regulators. Objectives: examine possibility Hypoxia inducible 1α (Hif1α) required Methods: CRISPR/Cas9 was used generate new loss-of-function alleles gene similar ( ), which encodes sole Hif1α. mutant strains were analyzed using combination metabolomics RNAseq Results: Our studies reveal phenotypes mimic those displayed Conclusions: These Sima/HIF1α embryogenesis up-regulate preparation Notably, study reveals Sima-dependent profile shares considerable overlap observed mutant, suggesting embryonic expression. melanogaster larvae exhibit severe second instar. same Estrogen Related ) mutants, other.

Language: Английский

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Cell type-specific driver lines targeting the Drosophila central complex and their use to investigate neuropeptide expression and sleep regulation

Published: Jan. 21, 2025

The central complex (CX) plays a key role in many higher-order functions of the insect brain including navigation and activity regulation. Genetic tools for manipulating individual cell types, knowledge what neurotransmitters neuromodulators they express, will be required to gain mechanistic understanding how these are implemented. We generated characterized split-GAL4 driver lines that express or small subsets about half CX types. surveyed neuropeptide receptor expression using fluorescent situ hybridization. About neuropeptides we examined were expressed only few cells, while rest dozens hundreds cells. Neuropeptide receptors more broadly at lower levels. Using our GAL4 drivers mark found 51 85 types least one 21 multiple neuropeptides. Surprisingly, all co-expressed neurotransmitter. Finally, used identify whose activation affects sleep, identified other link circadian clock CX. well-characterized genetic information on neurotransmitter provide should enhance studies

Language: Английский

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Standardized pipelines support and facilitate integration of diverse datasets at the Rat Genome Database

Database, Journal Year: 2025, Volume and Issue: 2025

Published: Jan. 1, 2025

Abstract The Rat Genome Database (RGD) is a multispecies knowledgebase which integrates genetic, multiomic, phenotypic, and disease data across 10 mammalian species. To support cross-species, multiomics studies to enhance expand on manually extracted from the biomedical literature by RGD team of expert curators, imports multiple sources. These include major databases substantial number domain-specific resources, as well direct submissions individual researchers. incorporation these diverse datatypes handled growing list automated import, export, processing, quality control pipelines. This article outlines development over time standardized infrastructure for pipelines with summary key design decisions focus lessons learned.

Language: Английский

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Animal models of kabuki syndrome and their applicability to novel drug discovery

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Kabuki Syndrome (KS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability, and multiple congenital anomalies. It caused pathogenic variants in the KMT2D KDM6A genes. Despite its significant disease burden, there are currently no approved therapies for KS, highlighting need advanced research therapeutic development. This review examines use of animal models KS research, including mice, fish, frogs, nematodes. These replicate key mechanistic clinical aspects Syndrome, facilitating preclinical studies to demonstrate efficacy. The literature search focused on identifying that utilized these investigate pathophysiology evaluate potential treatments. Refining essential enhance their relevance human accelerate development effective Syndrome. Insights from invaluable understanding underlying molecular mechanisms targets. Continued collaboration crucial translating findings into practice, offering hope future

Language: Английский

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Hypoxia-inducible factor 1α is required to establish the larval glycolytic program in Drosophila melanogaster

Molecular Metabolism, Journal Year: 2025, Volume and Issue: 93, P. 102106 - 102106

Published: Jan. 31, 2025

Language: Английский

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Innate Immunity in Insects: The Lights and Shadows of Phenoloxidase System Activation

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1320 - 1320

Published: Feb. 4, 2025

Melanogenesis and melanin deposition are processes essential for the effective immune response of insects to various invaders. Phenoloxidase (PO), produced in specialized cells as an inactive precursor prophenoloxidase (proPO), is key enzyme formation. The activated via limited proteolysis by a dedicated serine proteinase, which final element cascade proteinases (SPs) that make up PO system. provides different cytotoxic molecules active fighting infections, well melanin, important sequestration However, since reactive compounds generated during melanization also pose threat host cells, strict control system necessary self-protection. Different pathogens parasites influence through strategies, allow them survive develop insect body. In this review, we characterize “the lights shadows” activation, indicating, on one hand, its advantages efficient mechanism and, other dangers associated with improper functioning selected strategies regulating activity entomopathogenic organisms.

Language: Английский

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