A genome engineered tool set forDrosophilaTGF-β/BMP signaling studies DOI
Clara-Maria Ell, Abu Safyan, Mrinal Chayengia

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Abstract Ligands of the TGF-β/BMP superfamily are critically involved in regulation growth, patterning and organogenesis can act as long-range morphogens. Essential for understanding signaling dynamics tools that allow monitoring manipulating pathway components expressed at physiological levels endogenous spatiotemporal patterns. We used genome engineering to generate a comprehensive library endogenously epitope-or fluorescently-tagged versions receptors, co-receptors, transcription factors key feedback regulators Drosophila BMP Activin pathways. demonstrate generated alleles biologically active be utilized assessing tissue subcellular distribution corresponding proteins. Further, we show genomic platforms locus structure-function cis -regulatory analyses. Finally, present complementary set protein binder-based tools, which visualization well manipulation stability localization epitope-tagged proteins, providing new analysis beyond.

Language: Английский

Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis DOI Creative Commons
Alberto González-González,

Itzíar Álvarez-Iglesias,

Daniel García‐Sánchez

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Osteoporosis (OP), characterized by reduced bone mass and mineral density, is a global metabolic disorder that severely impacts the quality of life in affected individuals. Although current pharmacological treatments are effective, their long-term use often associated with adverse effects, highlighting need for safer, more sustainable therapeutic strategies. This study investigates pro-osteogenic anti-resorptive potential secretome from Smurf1-silenced mesenchymal stem cells (MSCs) as promising cell-free therapy regeneration. Conditioned media (CM) rat (rCM-Smur1) human MSCs (hCM-Smurf1) was collected analyzed. Pro-osteogenic assessed measuring vitro mineralization cultures. In vivo, studies were conducted using ectopic formation model post-menopausal osteoporotic mouse model. Additionally, primary preconditioned hCM-Smurf1, osteogenic capacity compared to induced BMP2 treatment. Ex explants treated hCM-Smurf1 assess effects. Proteomic analysis soluble vesicular CM fractions identified key proteins involved significantly enhanced vivo. Preconditioning increases mineralization, levels comparable those achieved ex vivo cultures, treatment RANKL expression without affecting OPG levels, indicating an effect. increased model, its local administration trabecular loss 50% after single within just four weeks. revealed both enriched essential ossification extracellular matrix organization, enhancing differentiation. The MSCs' shows potent reducing loss. provides compelling evidence MSC-derived non-toxic targeted osteoporosis. These findings warrant further clinical trials validate efficacy safety.

Language: Английский

Citations

1
Conservation and Evolution of Gene Networks Driving Development DOI
Helena Araujo, Daniel Bressan

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Editorial: Tissue regeneration using dental stem cells DOI Creative Commons
Marco Tatullo, Ian Ellis, Mohammad Islam

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 22, 2024

EDITORIAL article Front. Cell Dev. Biol., 22 March 2024Sec. Stem Research Volume 12 - 2024 | https://doi.org/10.3389/fcell.2024.1401476

Language: Английский

Citations

2
Chordin-mediated BMP shuttling patterns the secondary body axis in a cnidarian DOI Creative Commons
David Mörsdorf,

Maria Mandela Prünster,

Grigory Genikhovich

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 28, 2024

Abstract BMP signaling patterns secondary body axes throughout Bilateria and, strikingly, in the bilaterally symmetric corals and sea anemones – members of bilaterian sister clade Cnidaria. It has been suggested that secondary, “directive” axis anemone Nematostella vectensis requires Chordin-mediated “shuttling” ligands, like Drosophila or frog, however, an alternative “local inhibition” model is also possible. To choose between these two options, we generated localized Chordin sources morphant background showed presence ligands , mobile necessary sufficient to establish a peak at side embryo opposing source. In contrast, membrane-tethered Chordin-CD2 promotes weak within These results provide first mechanistic evidence for shuttling cnidarian suggest may have functional cnidarian-bilaterian ancestor.

Language: Английский

Citations

1
RNF43 and ZNRF3: Versatile regulators at the membrane and their role in cancer DOI Creative Commons
Shanshan Li, Jiahui Niu, Ron Smits

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: unknown, P. 189217 - 189217

Published: Nov. 1, 2024

Language: Английский

Citations

1
Postsynaptic BMP signaling regulates myonuclear properties in Drosophila larval muscles DOI Creative Commons
Victoria E. von Saucken,

Stefanie E. Windner,

Mary K. Baylies

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 11, 2024

Abstract The syncytial mammalian muscle fiber contains a heterogeneous population of (myo)nuclei. At the neuromuscular junction (NMJ), myonuclei have specialized positioning and gene expression. However, it remains unclear how are recruited what regulates myonuclear output at NMJ. Here, we identify specific properties located near Drosophila larval These synaptic increased size in relation to their surrounding cytoplasmic domain (scaling), DNA content (ploidy), levels transcription factor pMad, readout for BMP signaling activity. Our genetic manipulations show local affects size, nuclear ploidy, NMJ function. In support, RNA sequencing analysis reveals that pMad genes involved growth, ploidy (i.e., E2f1 ), neurotransmission. data suggest instructs then positively shapes synapse. This study deepens our understanding heterogeneity supports demands fine tune cellular function Summary (NMJ) is well characterized synapse, yet postsynaptic contributions allow synapse not understood. by von Saucken et al . uses define (myo)nuclei determine these properties.

Language: Английский

Citations

0
Postsynaptic BMP signaling regulates myonuclear properties in Drosophila larval muscles DOI
Victoria E. von Saucken,

Stefanie E. Windner,

Giovanna Armetta

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(1)

Published: Oct. 30, 2024

The syncytial mammalian muscle fiber contains a heterogeneous population of (myo)nuclei. At the neuromuscular junction (NMJ), myonuclei have specialized positioning and gene expression. However, it remains unclear how are recruited what regulates myonuclear output at NMJ. Here, we identify specific properties located near Drosophila larval These synaptic increased size in relation to their surrounding cytoplasmic domain (size scaling), DNA content (ploidy), levels transcription factor pMad, readout for BMP signaling activity. Our genetic manipulations show that local affects size, nuclear ploidy, NMJ function. In support, RNA sequencing analysis reveals pMad genes involved growth, ploidy (i.e., E2f1), neurotransmission. data suggest instructs positively shapes synapse. This study deepens our understanding heterogeneity supports demands fine tune cellular function

Language: Английский

Citations

0
A genome engineered tool set for Drosophila TGF-β/BMP signaling studies DOI Creative Commons
Clara-Maria Ell, Abu Safyan, Mrinal Chayengia

et al.

Development, Journal Year: 2024, Volume and Issue: 151(22)

Published: Nov. 4, 2024

Ligands of the TGF-β/BMP superfamily are crucially involved in regulation growth, patterning and organogenesis can act as long-range morphogens. Essential for understanding signaling dynamics tools that allow monitoring manipulating pathway components at physiological expression levels endogenous spatiotemporal patterns. We used genome engineering to generate a comprehensive library endogenously epitope- or fluorescent-tagged versions receptors, co-receptors, transcription factors key feedback regulators Drosophila BMP Activin pathways. demonstrate generated alleles biologically active be assessing tissue subcellular distribution corresponding proteins. Furthermore, we show genomic platforms locus structure-function cis-regulatory analyses. Finally, present complementary set protein binder-based tools, which visualization well manipulation stability localization epitope-tagged proteins, providing new analysis beyond.

Language: Английский

Citations

0
Long-Read Sequencing Reveals Increased Isoform Diversity in Key Transcription Factor Effectors of Intercellular Signalling at the Invertebrate-Vertebrate Transition DOI Creative Commons
Nuria P. Torres‐Aguila, Marika Salonna, Sebastian M. Shimeld

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Abstract Several intercellular signalling pathways (namely wingless - Wnt, Hedgehog Hh, and Bone Morphogenetic Protein BMP) are used repeatedly in animals throughout development evolution, also frequent targets for disease-associated disruptions. We have previously shown that the major transcriptional effectors of β-catenin-dependent Wnt signalling, TCF/LEF proteins, contrast to other pathway components, a higher gene number isoform diversity vertebrates versus invertebrates, but this increased has only been poorly quantified. Considering correlates with organism complexity, any increase is likely made significant contribution vertebrate evolution. Using de novo long-read transcriptomes, we compared per chordates Ciona intestinalis, Lampetra planeri Xenopus tropicalis , thus encompassing invertebrate sister group vertebrates, as well cyclostome gnathostome vertebrate. Our results implicate an transcription factors having disproportionate role evolutionary origin diversification vertebrates.

Language: Английский

Citations

0
The modulatory role of bone morphogenetic protein signaling in cerebellar synaptic plasticity DOI Open Access
Moritoshi Hirono,

Moeko Kudo,

Masahisa Yamada

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 169(1)

Published: Dec. 16, 2024

Abstract Bone morphogenetic proteins (BMPs), regulators of bone formation, have been implicated in embryogenesis and morphogenesis various tissues organs. BMP signaling plays a role the formation appropriate synaptic connections development normal neural circuits brain. However, physiological roles postnatal functions, including plasticity, remain largely unknown. Long‐term depression (LTD) transmission at parallel fiber (PF)‐Purkinje cell (PC) synapses cerebellum has suggested one neuronal mechanism underlying cerebellar functions. Here, we explored contribution to induction mouse LTD. We first demonstrated that BMP2 and/or 4 were expressed GABAergic neurons mature networks cortex. mRNA encoding receptor type 1B ( Bmpr1b ) was PC layer. Exogenous application noggin, ligand inhibitor, suppressed LTD by conjunctive stimulation, which caused under control condition. Furthermore, mice deficient BMPR1B exhibited attenuation extent induction, whereas they showed excitatory PF‐PC synapses. These results suggest after development, activated BMPR1B, layer, crucial facilitation LTD, leading modulation functions behaviors. image

Language: Английский

Citations

0