Maintenance of neuronal differentiation during development
Lead Research Organisation:
Imperial College London
Department Name: Life Sciences
Abstract
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Organisations
People |
ORCID iD |
| Tony Southall (Primary Supervisor) |
Publications
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011178/1 | 30/09/2015 | 25/02/2025 | |||
| 1656706 | Studentship | BB/M011178/1 | 02/10/2015 | 29/09/2019 |
| Description | Condensin complex has a crucial role in compacting DNA into chromosome during cell division, but its role in post-mitotic cells remains unexplored. In this work we described a novel role for condensin I subunit Cap-G in neurons. We characterised Cap-G expression pattern and localisation in the Drosophila central nervous system in vivo. To understand the function of Cap-G in neurons we generated cell-specific knock-down of Cap-G in neurons. Removal of Cap-G from post-mitotic neurons surprisingly resulted in severe developmental arrest, behavioural defects and an overall disruption in gene expression in the CNS. This is the first known effect of a condensin subunit in a post-mitotic neuron. I investigated whether Cap-G had a neuron-specific role in Drosophila, so I characterised Cap-G DNA binding profiles in neuronal stem cells and neurons, identifying dynamic, cell-specific binding of Cap-G in the CNS. Cap-G binding was depleted at accessible chromatin and known enhancer regions but highly enriched at repressive chromatin sites. Cap-G appears to have a cell-specific gene regulatory role in neurons. Knockdown animals exhibited a downregulation of neuron-specific genes and an upregulation of ectopic, non-CNS- specific genes. Genes bound by Cap-G significantly overlap with the disrupted genes detected in knockdown animals. This works provides novel evidence that condensin I subunit Cap-G in neurons is necessary for healthy nervous system development, transcriptome stability and maintenance of neuronal identity. |
| Exploitation Route | The discovery of a post-mitotic role for Cap-G highlights the importance in studying these chromatin associating proteins in a post-mitotic context to understand their role in development beyond cell division. Cell-binding data and RNA-seq data is freely accessible and can be used by other researchers if required. Fly lines generated are also available upon request. |
| Sectors | Other |
| URL | https://www.biorxiv.org/content/10.1101/2020.01.14.904409v1.article-metrics |