C. elegans cnd-1/NeuroD1 functions with the Hox gene ceh-13/labial to control multiple genes required for nervous system development and function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA515039 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8440440.fastq.gz | Fastqsanger.gz | |||
| SRR8440441.fastq.gz | Fastqsanger.gz | |||
| SRR8440442.fastq.gz | Fastqsanger.gz | |||
| SRR8440437.fastq.gz | Fastqsanger.gz | |||
| SRR8440438.fastq.gz | Fastqsanger.gz |
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Project description:Identifying the mechanisms behind neuronal fate specification are key to understanding neurodevelopmental disorders such as autism and schizophrenia. In vivo nervous system fate specification is difficult to study in vertebrates. However, the nematode Caenorhabditis elegans, with its invariant cell lineage and simple nervous system of 302 neurons, is an ideal organism to explore the earliest stages of neural development. We took a comparative transcriptome approach to understanding the role of cnd-1/NeuroD1 in C. elegans nervous system development and function. This basic helix-loop-helix transcription factor is deeply conserved across phyla, and plays a crucial role in cell fate specification in both the vertebrate nervous system and pancreas. We find that cnd-1 partially represses its own expression during C. elegans embryogenesis. In addition, we show that cnd-1 controls the expression of ceh-5, a Vax2-like homeobox class transcription factor expressed in the nervous system and in head muscles. We also demonstrate a role for the Hox gene ceh-13/labial in defining the fate of cnd-1-expressing motorneurons. Finally, we show that cnd-1 also controls the expression levels of genes required for post-mitotic function, including the RING-finger ubiquitin ligase rpm-1. These data highlight the utility of comparative transcriptomes for understanding the nuances of transcription factor control, and establish a paradigm for future transcriptome-based studies.
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2019-09-25 | PXD013584 | Pride
Project description:Identifying the mechanisms behind neuronal fate specification are key to understanding normal neural development in addition to neurodevelopmental disorders such as autism and schizophrenia. In vivo cell fate specification is difficult to study in vertebrates. However, the nematode Caenorhabditis elegans, with its invariant cell lineage and simple nervous system of 302 neurons, is an ideal organism to explore the earliest stages of neural development. We used a comparative transcriptome approach to examine the role of cnd-1/NeuroD1 in C. elegans nervous system development and function. This basic helix-loop-helix transcription factor is deeply conserved across phyla and plays a crucial role in cell fate specification in both the vertebrate nervous system and pancreas. We find that cnd-1 controls expression of ceh-5, a Vax2-like homeobox class transcription factor, in the RME head motorneurons and PVQ tail interneurons. We also show that cnd-1 functions redundantly with the Hox gene ceh-13/labial in defining the fate of DD1 and DD2 embryonic ventral nerve cord motorneurons. These data highlight the utility of comparative transcriptomes for identifying transcription factor targets and understanding gene regulatory networks.
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Project description:Astrocytes, the most abundant glial cells in the central nervous system (CNS), play a critical role in brain injury responses. While NeuroD1 overexpression in astrocytes has been shown to reverse glial scar formation and promote tissue repair in mouse models of traumatic brain injury (TBI), the underlying molecular mechanisms remain incompletely understood. To address this, we performed single-cell transcriptomic analysis on a controlled cortical impact (CCI) mouse model using recombinant adeno-associated virus (rAAV)-mediated astrocyte-specific NeuroD1 overexpression.Our findings demonstrate that NeuroD1 overexpression suppresses microglial activation and mitigates brain damage post-TBI. Single-cell RNA sequencing revealed significant shifts in astrocyte subtypes, with upregulated neuroinflammatory pathways and downregulated oxygen metabolism in TBI mice. Conversely, NeuroD1 overexpression reshaped astrocyte subpopulation dynamics, enhanced oxygen metabolism-related gene expression, and attenuated neuroinflammatory signaling. This study provides a comprehensive transcriptomic dataset detailing cellular and astrocyte subtype-specific changes following NeuroD1-mediated brain repair. These insights advance our understanding of cell fate modulation in TBI and support the development of NeuroD1-based gene therapies, offering a valuable resource for future TBI research and therapeutic strategies.
2025-11-01 | GSE305371 | GEO
Project description:modENCODE_submission_3068 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP500(official name : OP500 genotype : unc119(ed3);wgIs500(ceh-26::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Dresden using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-26::EGFP fusion protein is expressed in the correct ceh-26 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-26 transcription factor. made_by : R. Waterston ); Developmental Stage: late embryo; Genotype: unc119(ed3);wgIs500(ceh-26::TY1 EGFP FLAG;unc119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage late embryo; Target gene ceh-26; Strain OP500(official name : OP500 genotype : unc119(ed3);wgIs500(ceh-26::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Dresden using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-26::EGFP fusion protein is expressed in the correct ceh-26 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-26 transcription factor. made_by : R. Waterston ); temp (temperature) 20 degree celsius
2012-05-07 | E-GEOD-37798 | biostudies-arrayexpress
Project description:modENCODE_submission_3858 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP169(official name : OP169 genotype : unc119(ed3);wgIs169(ceh-39::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-39::EGFP fusion protein is expressed in the correct ceh-39 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-39 transcription factor. made_by : Unknown ); Developmental Stage: embryo; Genotype: unc119(ed3);wgIs169(ceh-39::TY1 EGFP FLAG;unc119); Sex: mixed Male and Hermaphrodite population; EXPERIMENTAL FACTORS: Developmental Stage embryo; Target gene ceh-39; Strain OP169(official name : OP169 genotype : unc119(ed3);wgIs169(ceh-39::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-39::EGFP fusion protein is expressed in the correct ceh-39 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-39 transcription factor. made_by : Unknown ); temp (temperature) 20 degree celsius
2013-07-11 | E-GEOD-48724 | biostudies-arrayexpress
Project description:modENCODE_submission_3209 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP82(official name : OP82 genotype : unc119(ed3);wgIs82(ceh-16::TY1 EGFP FLAG;unc119) outcross : 0 mutagen : None tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-16::EGFP fusion protein is expressed in the correct CEH-16 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-16 transcription factor. made_by : Bob Waterston's lab from UW ); Developmental Stage: L2; Genotype: unc119(ed3);wgIs82(ceh-16::TY1 EGFP FLAG;unc119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L2; Target gene ceh-16; Strain OP82(official name : OP82 genotype : unc119(ed3);wgIs82(ceh-16::TY1 EGFP FLAG;unc119) outcross : 0 mutagen : None tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-16::EGFP fusion protein is expressed in the correct CEH-16 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-16 transcription factor. made_by : Bob Waterston's lab from UW ); temp (temperature) 20 degree celsius
2013-07-11 | E-GEOD-48695 | biostudies-arrayexpress
Project description:NeuroD1 encodes a basic helix-loop-helix transcription factor involved in the development of neural and endocrine structures. NeuroD1 mRNA is highly abundant in the adult mammalian pineal gland and exhibits a developmental expression pattern similar to the retina. This is consistent with the common evolutionary origin of pinealocytes and retinal photoreceptors. Pinealocytes and retinal photoreceptors express a shared set of phototransduction genes and submammalian pinealocytes are photosensitive. In contrast to the retina, the pineal gland is a relatively homogeneous structure, composed 95% of pinealocytes. This makes the pineal gland a particularly useful model for understanding photoreceptor cell biology. The loss of NeuroD1 in the retina results in progressive photoreceptor degeneration and the molecular mechanisms underlying this retinal degeneration phenotype remain unknown. Similarly, the role that NeuroD1 plays in the pineal gland is unknown. To determine the function of NeuroD1 in the pineal gland and retina, a Cre/loxP recombination strategy was used to selectively target a NeuroD1 floxed allele and generate NeuroD1 conditional knockout (cKO) mice. Tissue specificity was conferred using Cre recombinase expressed under the control of the promoter of Crx, a transcription factor selectively expressed in the pineal gland and retina. Pineal and retinal tissues from two-month-old NeuroD1 cKO and control animals were used in microarray studies to identify candidate genes responsible for the photoreceptor degeneration phenotype. The Cre/loxP recombination strategy was used to target a NeuroD1 floxed allele and generate NeuroD1 conditional knockout mice (NeuroD1floxed::Crx-Cre+/-). NeuroD1 floxed mice (NeuroD1floxed::Crx-Cre-/-) served as the controls. Pineal glands and retinas from two-month-old control and conditional knockout mice were collected at ZT6 and ZT20. 3 pools of 6 pineal glands per genotype and respective time of day were collected for each sample. Similarly, 3 pools of 6 retinas each were also collected. RNA from each pool was extracted and hybridized on the Affymetrix Mouse 430 2.0 array.
2012-07-25 | E-GEOD-35396 | biostudies-arrayexpress
Project description:modENCODE_submission_2620 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP120(made_by : R Waterston description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-30::EGFP fusion protein is expressed in the correct ceh-30 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-30 transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc119(ed3);wgIs120(ceh-30::TY1 EGFP FLAG;unc119) official name : OP120 ); Developmental Stage: late embryo; Genotype: unc119(ed3);wgIs120(ceh-30::TY1 EGFP FLAG;unc119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage late embryo; Target gene ceh-30; Strain OP120(made_by : R Waterston description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-30::EGFP fusion protein is expressed in the correct ceh-30 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-30 transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc119(ed3);wgIs120(ceh-30::TY1 EGFP FLAG;unc119) official name : OP120 ); temp (temperature) 20 degree celsius Series_type: CHIP-seq
2011-02-18 | E-GEOD-25808 | biostudies-arrayexpress
Project description:Astrocytes, the most abundant glial cells in the central nervous system (CNS), play a critical role in brain injury responses. While NeuroD1 overexpression in astrocytes has been shown to reverse glial scar formation and promote tissue repair in mouse models of traumatic brain injury (TBI), the underlying molecular mechanisms remain incompletely understood.
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