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Self-organised pattern formation in the developing dorsal neural tube by a temporal relay of BMP signalling

ABSTRACT: Self-organised pattern formation in the developing dorsal neural tube by a temporal relay of BMP signalling

PROVIDER: PRJNA1036160 | ENA |

REPOSITORIES: ENA

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Self-organised pattern formation in the developing dorsal neural tube by a temporal relay of BMP signalling

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

Temporal control of BMP signalling determines neuronal subtype identity in the dorsal neural tube.

Project description:The conventional explanation for how a morphogen patterns a tissue holds that cells interpret different concentrations of an extrinsic ligand by producing corresponding levels of intracellular signalling activity, which in turn regulate differential gene expression. However, this view has been challenged, raising the possibility that distinct mechanisms are used to interpret different morphogens. Here, we investigate graded BMP signalling in the vertebrate neural tube. We show that defined exposure times to Bmp4 generate distinct levels of signalling and induce specific dorsal identities. Moreover, we provide evidence that a dynamic gradient of BMP activity confers progressively more dorsal neural identities in vivo. These results highlight a strategy for morphogen interpretation in which the tight temporal control of signalling is important for the spatial pattern of cellular differentiation.

| S-EPMC3596990 | biostudies-literature

Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling

Project description:We directed mESCs towards the dorsal sensory interneurons (dIs) using RA-/+ BMP4 and tested the effects of an axon guidance molecule netrin1 on dI differentiation in vitro. Using bulk-RNA seq analysis, we investiagted when the addition of netrin 1 will affect the transcriptome of differentiating dIs. For this analysis, we used three timewindows (conditions 1-3) for netrin addition (1) condition 1 netrin 1 was added together with RA+BMP4 at day 4, and RNA seq was conducted at day 5, (2) netrin1 was added after the RA+BMP4 mediated patterning at day 5 and RNA seq was conducted at day 6, and (3) netrin1 was added for the extended duration between day 5-day9 to investigate the netrin1 effects throughout the dI differentiation and RNA seq was conducted at day 9. Through this analysis we identified that netrin1 downregulate BMP signaling pathway, possibly through modlulating the mRNA processing of key mediator of BMP signaling such as Id genes and BMP signaling inhibitor Smad7 and affect dI differentiation. This is the first report to show that netrin1 regulate dI fate specification in the dorsal spinal cord.

2024-04-23 | GSE246903 | GEO

Construction of a dorsal-ventral patterned neural tube organoid from pluripotent stem cells.

Project description:Purpose: Characterization of cell types in wild-type and TCTN2 KO human neural tube organoids (hNTOs). Methods: Wild-type and TCTN2 KO hNTOs were harvested at day11. Libraries were prepared using Single Cell 3′Library & gel Bead kit v3.1 (10x Genomics, Cat# PN-1000121) according to the manufacturer’s protocol for 10000 cells recovery. Results: 13 neural progenitor cells were detected in wild-type hNTOs, and TCTN2 deficiency led to reduction of ventral progenitors cells. Conclusions: A well-organized nueral tube organoid was constructed by applying BMP and SHH morphogen gradients.

2024-02-06 | GSE254817 | GEO

Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling

Project description:Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling

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Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

Project description:Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

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Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

Project description:Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

| PRJNA991548 | ENA

Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

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

Genome-wide RNA expression analysis of rat dorsal root ganglion tissue after local absorbable collagen sponge implantation and BMP-2 exposure

Project description:Analysis of whole dorsal root ganglion tissue expression signatures in responses to absorbable collagen sponge implantation with and without BMP-2 exposure. The hypothesis is that inflammatory macrophage-associated responses to ACS implantation contributes to nociception in the DRG and spinal nerve.

2017-01-27 | GSE77384 | GEO

Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

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

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