Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition
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PROVIDER: PRJNA991548 | ENA |
REPOSITORIES: ENA
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Project description:Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition
| PRJNA1082271 | ENA
Project description:Organoids can undergo pattern formation by spontaneously forming spatially-localised signaling centers called organisers. Understanding how molecular pathways participate in this regulative process is a central challenge in biology. Here, we investigated self-organisation of a SHH-expressing floorplate in clonal neural tube organoids (NTOs). In NTOs, a pulse of retinoic acid (RA) applied at Day 2 triggers self-organisation of a FOXA2+ floorplate by Day 6. FOXA2 expression was initially spatially scattered before resolving into multiple clusters. These FOXA2+ clusters underwent competition and physical sorting, resulting in a stable “winning” floorplate. We identified BMP signalling as a key governor of long-range cluster competition.
2024-04-23 | GSE236543 | GEO
Project description:The neural tube (NT) has been a hallmark example of embryonic induction and patterning whereby the notochord induces an organiser, the floorplate, that secretes Sonic Hedgehog (SHH) to pattern the surrounding field of neural progenitors. On the other hand, NT organoids (NTOs) formed from embryonic stem cells (ESCs) undergo spontaneous floorplate formation and patterning in the absence of their normal embryonic inducers. Understanding how stem cells undergo regulative organiser formation is a central challenge in biology. Here, we investigated the self-organisation of a SHH-expressing floorplate organiser using clonal mouse NTOs. Expression of FOXA2, a floorplate transcription factor, was initially spatially scattered before resolving into multiple clusters. These FOXA2+ clusters underwent competition and physical sorting, resulting in a stable “winning” floorplate. We identified BMP signalling as a key governor of long-range cluster competition. FOXA2+ clusters expressed BMP4 ligand suppressing FOXA2 in receiving cells, while simultaneously expressing the BMP-inhibitor NOGGIN to secure FOXA2+ cluster survival. Genetic mutation of Noggin perturbed the floorplate not only in NTOs but also in vivo at the mid-hindbrain region of the mouse NT. These results demonstrate how the floorplate can form autonomously without its well-known inducer, the notochord, suggesting redundant mechanisms ensuring robustness. Defining molecular pathways that govern organiser self-organisation is critical in harnessing the developmental plasticity of stem cells toward directed tissue engineering.
2024-04-23 | GSE260579 | GEO
Project description:Developing tissues interpret dynamic changes in morphogen activity to generate cell type diversity. To quantitatively study BMP signalling dynamicsin the vertebrateneural tube, we developed a new ES cell differentiation systemtailored for growing tissues. Differentiating cellsform strikingself-organised pattern of dorsal neural tube cell typesdriven by sequential phases of BMP signalling that are observed both in vitro and in vivo.Data-driven biophysical modelling showed that thesedynamics result from coupling fast negative feedbackwithslow positive regulation of signalling bythe specification of an endogenousBMP source.Thus, in contrast to relays that propagate morphogen signalling in space, we uncover a BMP signallingrelay that operates intime. This mechanism allows rapid initial concentration-sensitive response that is robustly terminated, thereby regulating balanced sequential cell type generation.Altogether, our study provides an experimental and theoretical framework to understand how signalling dynamicsis exploited indeveloping tissues.
2024-08-19 | GSE247069 | GEO
Project description:During host cell invasion, microsporidia translocate their entire cytoplasmic contents through a thin, hollow superstructure known as the polar tube. To achieve this, the polar tube transitions from a compact spring-like state inside the environmental spore to a long needle-like tube capable of longrange sporoplasm delivery. The unique mechanical properties of the building blocks of the polar tube allow for an explosive transition from compact to extended state and support the rapid cargo translocation process. The molecular and structural factors enabling this ultrafast process and the ultrastructural changes during cargo delivery remain a mystery. Here, we employ light microscopy and in situ cryo-electron tomography to visualize multiple ultrastructural states of the polar tube, allowing us to evaluate the kinetics of its germination and characterize the underlying morphological transitions. We describe a cargo-filled state with a unique ordered arrangement of microsporidian ribosomes, which cluster along the thin tube wall, and an empty post-translocation state with a reduced diameter but a thicker wall. Together with endogenous compositional information from an affinity-purified polar tube, our work provides comprehensive novel data on the infection apparatus of microsporidia and demonstrates that ribosomes are efficiently transported through polar tubes in a spiral-like parallel arrangement.
2024-01-09 | PXD042571 | Pride
Project description:Mindbomb1 is a Novel Negative Regulator of BMP Signaling.
2024-07-02 | MSV000095215 | MassIVE
Project description:We report the establishment of a stable 3D in vitro organoid culture procedure from human fallopian tube samples and confirming experimentally the existence of adult stem cells in this epithelial tissue. Long term growth and the differentiation of the organoids depend on the interplay between the paracrine signaling pathways Wnt, NOTCH and BMP, since R spondin 1 and Wnt3a are required for preservation of stemness in concert with continuous suppression of TGF-beta activity. Microarray analysis revealed that inhibition of NOTCH signaling by the gamma-secretase inhibitor DBZ leads to down-regulation of a gene cluster associated with pluripotency, as the adult stem cell signature is significantly enriched in the list of downregulated targets. Microarray experiments were performed as dual-color hybridizations on Agilent human whole genome catalog 44K arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied.
2015-01-01 | E-GEOD-60919 | biostudies-arrayexpress
Project description:We report the establishment of a stable 3D in vitro organoid culture procedure from human fallopian tube samples and confirming experimentally the existence of adult stem cells in this epithelial tissue. Long term growth and the differentiation of the organoids depend on the interplay between the paracrine signaling pathways Wnt, NOTCH and BMP, since R spondin 1 and Wnt3a are required for preservation of stemness in concert with continuous suppression of TGF-beta activity. Microarray analysis revealed that inhibition of NOTCH signaling by the gamma-secretase inhibitor DBZ leads to down-regulation of a gene cluster associated with pluripotency, as the adult stem cell signature is significantly enriched in the list of downregulated targets.
2015-01-01 | GSE60919 | GEO
Project description:In Drosophila, efferent neurons gain access to a target-derived BMP signal in the periphery that is required for differentiation and/or synaptic growth and neurotransmission. This requires transcriptional activity of the BMP-activated Smad transcription factors, but the Smad-bound enhancers and BMP-regulated effector genes they control remain unidentified. In the absence of insight into how BMP signaling controls these fundamental aspects of neuronal development and function, here we test whether Smads act directly at widely-deployed archetypal Smad-binding motifs to directly co-regulate batteries of BMP-responsive genes. To target these motifs for analysis, we employed a bioinformatics approach to identify candidate motifs conforming to the consensus 15bp BMP-Activation Element (BMP-AE). After filtering for high conservation and proximity to neuronally-expressed genes, we prioritized 62 BMP-AEs for analysis. Testing the in vivo enhancer activity of 58 genomic fragments containing these BMP-AEs in transgenic reporters, we show that 61% are functional BMP enhancers in diverse motoneuron and neuropeptidergic neuronal populations, and that the BMP-AE motif itself is required for activity. Moreover, 60% of these functional BMP-AEs were located within 20kb of at least one BMP activated gene, as identified by RNAseq analysis. Finally, we show that the BMP-AE motif plays a conserved activator function in the vertebrate nervous system, by electroporation in the developing chick neural tube. Our results provide evidence that BMP signaling controls neuronal development and function by directly coordinating networks of genes through widespread deployment of conserved, consensus Smad-binding motifs.
2018-10-25 | GSE106650 | GEO
Project description:Self-organised pattern formation in the developing dorsal neural tube by a temporal relay of BMP signalling
| PRJNA1036160 | ENA