1. Developmental Biology
Download icon

The Hox transcription factor Ubx stabilizes lineage commitment by suppressing cellular plasticity in Drosophila

  1. Katrin Domsch
  2. Julie Carnesecchi
  3. Vanessa Disela
  4. Jana Friedrich
  5. Nils Trost
  6. Olga Ermakova
  7. Maria Polychronidou
  8. Ingrid Lohmann  Is a corresponding author
  1. Centre for Organismal Studies, Heidelberg University, Germany
  2. EMBO, Germany
Research Article
  • Cited 7
  • Views 1,960
  • Annotations
Cite this article as: eLife 2019;8:e42675 doi: 10.7554/eLife.42675

Abstract

During development cells become restricted in their differentiation potential by repressing alternative cell fates, and the Polycomb complex plays a crucial role in this process. However, how alternative fate genes are lineage-specifically silenced is unclear. We studied Ultrabithorax, a multi-lineage transcription factor of the Hox class, in two tissue lineages using sorted nuclei and interfered with Ubx in mesodermal cells. We find that depletion of Ubx leads to the de-repression of genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by retaining the Polycomb Group protein Pleiohomeotic at Ubx targeted genomic regions, thereby stabilizing repressive chromatin marks in a lineage-dependent manner. Our study demonstrates that Ubx stabilizes lineage choice by suppressing the multipotency encoded in the genome via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it could set a block to transdifferentiation in adult cells.

Data availability

Sequencing data have been deposited in GEO: GSE121754 (all), GSE121670 (RNA-Seq) & GSE121752 (ChIP-Seq).

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

Article and author information

Author details

  1. Katrin Domsch

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  2. Julie Carnesecchi

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Vanessa Disela

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  4. Jana Friedrich

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  5. Nils Trost

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5171-018X

  6. Olga Ermakova

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  7. Maria Polychronidou

    Molecular Systems Biology, EMBO, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  8. Ingrid Lohmann

    Developmental Biology, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
    For correspondence
    ingrid.lohmann@cos.uni-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0918-2758

Funding

Deutsche Forschungsgemeinschaft (LO 844 8/1)

  • Ingrid Lohmann

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

Reviewing Editor

  1. Bruce Edgar, University of Utah, United States

Publication history

  1. Received: October 8, 2018
  2. Accepted: April 30, 2019
  3. Accepted Manuscript published: May 3, 2019 (version 1)
  4. Version of Record published: May 13, 2019 (version 2)
  5. Version of Record updated: May 16, 2019 (version 3)

Copyright

© 2019, Domsch 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

  • 1,960
    Page views
  • 336
    Downloads
  • 7
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Categories and tags

Research organism

Further reading

    1. Computational and Systems Biology
    2. Developmental Biology

    Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

    Emanuel Cura Costa et al.
    Research Advance

    Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modelling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during ~85 hours after amputation within ~830mm of the injury. We adapted FUCCI technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.

    1. Developmental Biology
    2. Evolutionary Biology

    Selection for increased tibia length in mice alters skull shape through parallel changes in developmental mechanisms

    Colton M Unger et al.
    Research Article Updated

    Bones in the vertebrate cranial base and limb skeleton grow by endochondral ossification, under the control of growth plates. Mechanisms of endochondral ossification are conserved across growth plates, which increases covariation in size and shape among bones, and in turn may lead to correlated changes in skeletal traits not under direct selection. We used micro-CT and geometric morphometrics to characterize shape changes in the cranium of the Longshanks mouse, which was selectively bred for longer tibiae. We show that Longshanks skulls became longer, flatter, and narrower in a stepwise process. Moreover, we show that these morphological changes likely resulted from developmental changes in the growth plates of the Longshanks cranial base, mirroring changes observed in its tibia. Thus, indirect and non-adaptive morphological changes can occur due to developmental overlap among distant skeletal elements, with important implications for interpreting the evolutionary history of vertebrate skeletal form.

    1. Developmental Biology
    2. Neuroscience

    DCC regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation

    Laura Morcom et al.
    Research Article Updated

    The forebrain hemispheres are predominantly separated during embryogenesis by the interhemispheric fissure (IHF). Radial astroglia remodel the IHF to form a continuous substrate between the hemispheres for midline crossing of the corpus callosum (CC) and hippocampal commissure (HC). Deleted in colorectal carcinoma (DCC) and netrin 1 (NTN1) are molecules that have an evolutionarily conserved function in commissural axon guidance. The CC and HC are absent in Dcc and Ntn1 knockout mice, while other commissures are only partially affected, suggesting an additional aetiology in forebrain commissure formation. Here, we find that these molecules play a critical role in regulating astroglial development and IHF remodelling during CC and HC formation. Human subjects with DCC mutations display disrupted IHF remodelling associated with CC and HC malformations. Thus, axon guidance molecules such as DCC and NTN1 first regulate the formation of a midline substrate for dorsal commissures prior to their role in regulating axonal growth and guidance across it.