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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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A gene regulatory network for neural induction

ABSTRACT: During early vertebrate development, signals from a special region of the embryo, the organizer, can re-direct the fate of non-neural ectoderm cells to form a complete, patterned nervous system. This is called neural induction and has generally been imagined as a single signaling event, causing a switch of fate. Here we undertake a comprehensive analysis, in very fine time-course, of the events following exposure of ectoderm to the organizer. Using transcriptomics and epigenomics we generate a Gene Regulatory Network comprising 175 transcriptional regulators and 5,614 predicted interactions between them, with fine temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization, single-cell RNA-sequencing and reporter assays we show that neural induction by a grafted organizer mimics normal neural plate development. The study is accompanied by a comprehensive resource including information about conservation of the predicted enhancers in different vertebrate systems.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Gallus gallus

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PROVIDER: E-MTAB-10420 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): E-MTAB-10424E-MTAB-10408

REPOSITORIES: biostudies-arrayexpress

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A gene regulatory network for neural induction

Project description:During early vertebrate development, signals from a special region of the embryo, the organizer, can re-direct the fate of non-neural ectoderm cells to form a complete, patterned nervous system. This is called neural induction and has generally been imagined as a single signaling event, causing a switch of fate. Here we undertake a comprehensive analysis, in very fine time-course, of the events following exposure of ectoderm to the organizer. Using transcriptomics and epigenomics we generate a Gene Regulatory Network comprising 175 transcriptional regulators and 5,614 predicted interactions between them, with fine temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization, single-cell RNA-sequencing and reporter assays we show that neural induction by a grafted organizer mimics normal neural plate development. The study is accompanied by a comprehensive resource including information about conservation of the predicted enhancers in different vertebrate systems.

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A gene regulatory network for neural induction

Project description:During early vertebrate development, signals from a special region of the embryo, the organizer, can re-direct the fate of non-neural ectoderm cells to form a complete, patterned nervous system. The process has generally been imagined as the result of a single signaling event, causing a simple switch. Here we undertake a comprehensive analysis, in very fine time-course, of the events following exposure of ectoderm to signals from the organizer. Using transcriptomics and epigenomics we generate a Gene Regulatory Network comprising 175 transcriptional regulators and 5,614 predicted interactions between them, with temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization and single-cell RNA-sequencing and reporter assays we show that neural induction by a grafted organizer mimics normal neural plate development. The study is accompanied by a comprehensive resource including information about conservation of the predicted enhancers in different vertebrate systems.

2023-03-14 | E-MTAB-10408 | biostudies-arrayexpress

10x single cell RNAseq of chick ectoderm from stages HH5 to ss4

Project description:The vertebrate ectoderm gives rise to a variety of cell lineages, including neural, neural crest, placodal and non-neural cell fates. How cell fates are specified at the neural plate border (the region surrounding the neural plate) is not fully understood. We therefore carried out 10x scRNAseq of the chick epiblast to investigate cell fate specification at the neural plate border. Embryos were dissected and pooled according to stage. The tissue was then dissociated and FAC sorted to remove dead cells and remaining doublets before cells were stored in MeOH. Due to the time required to dissect embryos, multiple rounds of collections were carried out, with collections from the same stage pooled prior to 10x sequencing. Libraries were sequenced using an Illumina HiSeq 4000 at the Francis Crick Institute, London. This collection was a follow up to E-MTAB-10408.

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Segregation of neural crest specific lineage trajectories from a heterogeneous neural plate border territory only emerges at neurulation

Project description:The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harbouring neural crest and cranial placode progenitors. Here we profile avian epiblast cells as a function of time using single-cell RNA-seq to define transcriptional changes in the emerging ‘neural plate border’. The results reveal gradual establishment of heterogeneous neural plate border signatures, including novel genes that we validate by fluorescent in situ hybridization. Developmental trajectory analysis shows that segregation of neural plate border lineages only commences at early neurulation, rather than at gastrulation as previously predicted. We find that cells expressing the prospective neural crest marker Pax7 contribute to multiple lineages, and a subset of premigratory neural crest cells shares a transcriptional signature with their border precursors. Together, our results suggest that cells at the neural plate border remain heterogeneous until early neurulation, at which time progenitors become progressively allocated toward defined lineages.

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Single-cell transcriptomics reveals the cellular identity of a novel progenitor population crucial for murine neural tube closure

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Project description:Congenital Heart Disease (CHD) is the most common birth defect and leading cause of infant mortality, yet molecular mechanisms explaining CHD remain mostly unknown. Sequencing studies are identifying CHD candidate genes at a brisk rate including MINK1, a serine/threonine kinase. However, a plausible molecular mechanism connecting CHD and MINK1 is unknown. Here, we reveal that mink1 is required for proper heart development due to its role in left right patterning. mink1 defines the cell fates of the Left-Right Organizer (LRO), a ciliated structure in the posterior mesoderm that breaks bilateral symmetry in vertebrate embryos. To identify mink1 targets, we applied an unbiased proteomics approach and identified the transcription factor, HMGA2. HMGA2 is necessary and sufficient for specifying Spemann’s Organizer, which can neuralize the ectoderm and dorsalize the mesoderm. Indeed, we demonstrate that HMGA2 is downstream of catenin, a critical effector of the Wnt signaling pathway that is well known to induce Spemann Organizer cell fates. In summary, we discover a transcription factor, HMGA2, that is downstream of mink1 that is critical for the specification of Spemann’s Organizer as well as the LRO defining a plausible mechanism for CHD.

2024-05-22 | PXD028827 | Pride

Fate specification of neural plate border by canonical Wnt signaling and Grhl3 is crucial for neural tube closure.

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From neural border epithelium to neural crest emigration: A comprehensive single cell roadmap of the timing and regulatory logic underlying cranial and vagal neural crest emergence [morpholinoRNAseq]

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