Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons

  1. Amira Hassan
  2. Pablo Araguas Rodriguez
  3. Stefan K Heidmann
  4. Emma L Walmsley
  5. Gabriel N Aughey  Is a corresponding author
  6. Tony D Southall  Is a corresponding author
  1. Imperial College London, United Kingdom
  2. University of Bayreuth, Germany

Abstract

Condensin complexes are essential for mitotic chromosome assembly and segregation during cell divisions, however, little is known about their functions in post-mitotic cells. Here we report a role for the condensin I subunit Cap-G in Drosophila neurons. We show that, despite not requiring condensin for mitotic chromosome compaction, post-mitotic neurons express Cap-G. Knockdown of Cap-G specifically in neurons (from their birth onwards) results in developmental arrest, behavioural defects, and dramatic gene expression changes, including reduced expression of a subset of neuronal genes and aberrant expression of genes that are not normally expressed in the developing brain. Knockdown of Cap-G in mature neurons results in similar phenotypes but to a lesser degree. Furthermore, we see dynamic binding of Cap-G at distinct loci in progenitor cells and differentiated neurons. Therefore, Cap-G is essential for proper gene expression in neurons and plays an important role during the early stages of neuronal development.

Data availability

All raw sequence files and processed files have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus (accession number GSE142112).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Amira Hassan

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Pablo Araguas Rodriguez

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Stefan K Heidmann

    Lehrstuhl für Genetik, University of Bayreuth, Bayreuth, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Emma L Walmsley

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3785-075X
  5. Gabriel N Aughey

    Department of Life Sciences, Imperial College London, London, United Kingdom
    For correspondence
    g.aughey@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5610-9345
  6. Tony D Southall

    Department of Life Sciences, Imperial College London, London, United Kingdom
    For correspondence
    t.southall@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8645-4198

Funding

Wellcome (104567/Z/14/Z)

  • Tony D Southall

Biotechnology and Biological Sciences Research Council (BB/P017924/1)

  • Gabriel N Aughey
  • Tony D Southall

Biotechnology and Biological Sciences Research Council (BB/M011178/1)

  • Amira Hassan

Deutsche Forschungsgemeinschaft (HE2354/23-2)

  • Stefan K Heidmann

Deutsche Forschungsgemeinschaft (HE2354/4-1)

  • Stefan K Heidmann

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Anne E West, Duke University School of Medicine, United States

Version history

  1. Received: January 14, 2020
  2. Accepted: April 6, 2020
  3. Accepted Manuscript published: April 7, 2020 (version 1)
  4. Version of Record published: April 20, 2020 (version 2)

Copyright

© 2020, Hassan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,663
    views
  • 184
    downloads
  • 11
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Amira Hassan
  2. Pablo Araguas Rodriguez
  3. Stefan K Heidmann
  4. Emma L Walmsley
  5. Gabriel N Aughey
  6. Tony D Southall
(2020)
Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons
eLife 9:e55159.
https://doi.org/10.7554/eLife.55159

Share this article

https://doi.org/10.7554/eLife.55159

Further reading

    1. Developmental Biology
    Siyuan Cheng, Ivan Fan Xia ... Stefania Nicoli
    Research Article

    Vascular smooth muscle cells (VSMCs) envelop vertebrate brain arteries and play a crucial role in regulating cerebral blood flow and neurovascular coupling. The dedifferentiation of VSMCs is implicated in cerebrovascular disease and neurodegeneration. Despite its importance, the process of VSMC differentiation on brain arteries during development remains inadequately characterized. Understanding this process could aid in reprogramming and regenerating dedifferentiated VSMCs in cerebrovascular diseases. In this study, we investigated VSMC differentiation on zebrafish circle of Willis (CoW), comprising major arteries that supply blood to the vertebrate brain. We observed that arterial specification of CoW endothelial cells (ECs) occurs after their migration from cranial venous plexus to form CoW arteries. Subsequently, acta2+ VSMCs differentiate from pdgfrb+ mural cell progenitors after they were recruited to CoW arteries. The progression of VSMC differentiation exhibits a spatiotemporal pattern, advancing from anterior to posterior CoW arteries. Analysis of blood flow suggests that earlier VSMC differentiation in anterior CoW arteries correlates with higher red blood cell velocity and wall shear stress. Furthermore, pulsatile flow induces differentiation of human brain PDGFRB+ mural cells into VSMCs, and blood flow is required for VSMC differentiation on zebrafish CoW arteries. Consistently, flow-responsive transcription factor klf2a is activated in ECs of CoW arteries prior to VSMC differentiation, and klf2a knockdown delays VSMC differentiation on anterior CoW arteries. In summary, our findings highlight blood flow activation of endothelial klf2a as a mechanism regulating initial VSMC differentiation on vertebrate brain arteries.

    1. Developmental Biology
    Zhimin Xu, Zhao Wang ... Yingchuan B Qi
    Research Article

    Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of lin-4 expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for lin-4 activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. MYRF-1 regulates lin-4 expression cell-autonomously and hyperactive MYRF-1 can prematurely drive lin-4 expression in embryos and young first-stage larvae. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.