Temporal transitions in post-mitotic neurons throughout the C. elegans nervous system [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA751424 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15329100.fastq.gz | Fastqsanger.gz | |||
| SRR15329101.fastq.gz | Fastqsanger.gz | |||
| SRR15329102.fastq.gz | Fastqsanger.gz | |||
| SRR15329103.fastq.gz | Fastqsanger.gz | |||
| SRR15329104.fastq.gz | Fastqsanger.gz |
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Project description:The nervous system of animals is functional at early postembryonic stages but undergoes extensive anatomical and functional changes throughout postembryonic development to eventually form a fully mature nervous system at adulthood. The molecular changes in post-mitotic neurons across post-embryonic development and the genetic programs that control these temporal transitions are not well understood. Using the model organism C. elegans, we comprehensively characterized the distinct functional states (locomotor behavior) and corresponding distinct molecular states (transcriptome) of the post-mitotic nervous system across temporal transitions from early post-embryonic periods to adulthood. We observed pervasive changes in gene expression, many of which controlled by the conserved heterochronic miRNA lin-4/mir-125 and its target, the transcription factor lin-14. The functional relevance of these molecular, lin-4/lin-14 controlled transitions are exemplified by a novel neuropeptide, nlp-45, which confers temporally controlled anti-exploratory activities. Our studies provide new insights into a perhaps generalizable regulatory mechanism that alters neuron-type specific gene batteries to modulate distinct behaviors states, and also provides a rich atlas of post-embryonic molecular changes to uncover additional regulatory mechanisms.
2021-10-25 | GSE158274 | GEO
Project description:The nervous system of animals is functional at early postembryonic stages but undergoes extensive anatomical and functional changes throughout postembryonic development to eventually form a fully mature nervous system at adulthood. The molecular changes in post-mitotic neurons across post-embryonic development and the genetic programs that control these temporal transitions are not well understood. Using the model organism C. elegans, we comprehensively characterized the distinct functional states (locomotor behavior) and corresponding distinct molecular states (transcriptome) of the post-mitotic nervous system across temporal transitions from early post-embryonic periods to adulthood. We observed pervasive changes in gene expression, many of which controlled by the conserved heterochronic miRNA lin-4/mir-125 and its target, the transcription factor lin-14. The functional relevance of these molecular, lin-4/lin-14 controlled transitions are exemplified by a novel neuropeptide, nlp-45, which confers temporally controlled anti-exploratory activities. Our studies provide new insights into a perhaps generalizable regulatory mechanism that alters neuron-type specific gene batteries to modulate distinct behaviors states, and also provides a rich atlas of post-embryonic molecular changes to uncover additional regulatory mechanisms.
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Project description:Temporal transitions in post-mitotic neurons throughout the C. elegans nervous system
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Project description:Background: Synaptic transmission is required for functional maturation of the CNS and to induce gene transcription involved in neuronal plasticity. Our aim is to identify genes that are transcriptionally regulated by synaptic transmission during development. cDNA microarrays will be used to compare gene expression in normal embryos and embryos with no synaptic transmission. Using the Gal4 UAS system, the tetanus toxin light fragment (TET) will be expressed throughout the nervous system. The effects of TET are well characterised: the synaptic protein n-Synaptobrevin is cleaved, blocking evokes vesicle fusion in TET expressing neurons and as a result synaptic transmission is blocked. Embryos expressing an inactive, mutant version of TET (iTET) show no detectable phenotype. Thus a comparison of gene expression in iTET expressing embryos and TET expressing embryos focuses our screen cleanly and specifically on genes that are regulated by synaptic transmission. At the end of larval life, during metamorphosis, there is a second phase of nervous system development with the same requirement for neural circuit differentiation and maturation as in the embryo. We will compare gene expression in TET expressing and iTET expressing pupae to identify genes which are regulated by synaptic transmission in this second phase of nervous system development. We will focus our analysis on genes which are similarly regulated in both systems. Plan: elav Gal4 (expressed in all the neurons) for the embryos and Heat Shock Gal4 (which allows a temporally controlled expression) for the pupae are used to drive UAS TET and UAS iTET throughout the nervous system. Crosses are set up with flies homozygous for Gal4 or UAS transgenes, so that all the progeny have the same genotype. Total RNA is extracted from 500 carefully staged embryos that have been collected at the time of hatching. Pupae are heat shocked at 24 hours after puparium formation, and heads are then collected 5 days after puparium formation. TET expressing pupae are paralysed but morphologically normal whereas iTET expressing pupae emerge as normal adults. Total RNA will be extracted from 250 heads of each genotype. Probes made from TET and iTET expressing embryos extracts will be hybridised together to the chip and so will be probes made from TET and iTET expressing pupae extracts. Genes regulated in both systems will be compared together.
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Project description:Mitotic bookmarking by CTCF and fast post-mitotic gene reactivation in ES cells
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Project description:Once generated, neurons are thought to permanently exit the cell cycle and become irreversibly differentiated. However, neither the precise point at which this post-mitotic state is attained nor the extent of its irreversibility is clearly defined. Here we report that newly born neurons from the upper layers of the mouse cortex, despite initiating axon and dendrite elongation, continue to drive gene expression from the neurogenic intermediate neural progenitor tubulin ?1 promoter (T?1p). These observations suggest an ambiguous post-mitotic neuronal state. Whole transcriptome analysis of sorted upper cortical neurons further revealed that neurons continue to express genes related to cell cycle progression long after mitotic exit until at least post-natal day 3 (P3). These genes are however down regulated thereafter and are associated with a concomitant up regulation of tumor suppressors at P5. Interestingly, newly born neurons located in the cortical plate (CP) at embryonic day 18-19 (E18-E19) and P3 challenged with calcium influx are found in S/G2/M phases of the cell cycle, and still able to undergo division at E18-E19 but not at P3. At P5 however, calcium influx becomes neurotoxic and leads instead to neuronal loss. Our data delineate for the first time the temporal window during which developing neurons acquire a post-mitotic state.
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Project description:Here we show sequential functions of CPEB1 and CPEB4 in the localization of repressed mRNAs to the mitotic spindle and their subsequent phase -specific activation to promote cell phase transitions and correct chromosome segregation.
2021-06-29 | GSE99810 | GEO
Project description:Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the significance and importance of their bookmarking function. Here, we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover an unexpected redundancy among members of the protein superfamily of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ESRRB is essential in maintaining pluripotency in mouse embryonic stem cells, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly the most rapidly and strongly reactivated ones. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.
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