1. Stem Cells and Regenerative Medicine

Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead

  1. Hideyuki Komori
  2. Qi Xiao
  3. Derek H Janssens
  4. Yali Dou
  5. Cheng-Yu Lee  Is a corresponding author
  1. University of Michigan Medical School, United States
https://doi.org/10.7554/eLife.03502
Share this article
Cite this article
  1. Hideyuki Komori
  2. Qi Xiao
  3. Derek H Janssens
  4. Yali Dou
  5. Cheng-Yu Lee
(2014)
Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead
eLife 3:e03502.
https://doi.org/10.7554/eLife.03502
  2. Download BibTex
  3. Download .RIS

Abstract

The mechanisms that maintain the functional heterogeneity of stem cells, which generates diverse differentiated cell types required for organogenesis, are not understood. Here, we report that Trithorax (Trx) actively maintains the heterogeneity of neural stem cells (neuroblasts) in the developing Drosophila larval brain. trx mutant type II neuroblasts gradually adopt a type I neuroblast functional identity, losing the competence to generate intermediate neural progenitors (INPs) and directly generating differentiated cells. Trx regulates a type II neuroblast functional identity in part by maintaining chromatin in the buttonhead (btd) locus in an active state through the histone methyltransferase activity of the SET1/MLL complex. Consistently, btd is necessary and sufficient for eliciting a type II neuroblast functional identity. Furthermore, over-expression of btd restores the competence to generate INPs in trx mutant type II neuroblasts. Thus, Trx instructs a type II neuroblast functional identity by epigenetically promoting Btd expression, thereby maintaining neuroblast functional heterogeneity.

Article and author information

Author details

  1. Hideyuki Komori

    University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Qi Xiao

    University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Derek H Janssens

    University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Yali Dou

    University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Cheng-Yu Lee

    University of Michigan Medical School, Ann Arbor, United States
    For correspondence
    leecheng@umich.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: May 28, 2014
  2. Accepted: October 3, 2014
  3. Accepted Manuscript published: October 6, 2014 (version 1)
  4. Version of Record published: November 6, 2014 (version 2)

Copyright

© 2014, Komori 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

  • 4,677
    Page views
  • 740
    Downloads
  • 16
    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)

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. Hideyuki Komori
  2. Qi Xiao
  3. Derek H Janssens
  4. Yali Dou
  5. Cheng-Yu Lee
(2014)
Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead
eLife 3:e03502.
https://doi.org/10.7554/eLife.03502

Categories and tags

Research organism

Further reading

    1. Developmental Biology
    2. Neuroscience

    The Drosophila Sp8 transcription factor Buttonhead prevents premature differentiation of intermediate neural progenitors

    Yonggang Xie et al.
    Research Article Updated

    Intermediate neural progenitor cells (INPs) need to avoid differentiation and cell cycle exit while maintaining restricted developmental potential, but mechanisms preventing differentiation and cell cycle exit of INPs are not well understood. In this study, we report that the Drosophila homolog of mammalian Sp8 transcription factor Buttonhead (Btd) prevents premature differentiation and cell cycle exit of INPs in Drosophila larval type II neuroblast (NB) lineages. We show that the loss of Btd leads to elimination of mature INPs due to premature differentiation of INPs into terminally dividing ganglion mother cells. We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs. We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs. Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.

    1. Stem Cells and Regenerative Medicine
    2. Developmental Biology

    Neuroblasts: Maintaining neural stem cell identity in the brain

    Yanrui Jiang, Heinrich Reichert
    Insight

    In the developing fruit fly brain, a protein called Trithorax increases the number of neural cells produced from a single stem cell, in part by regulating the transcription of the target genes buttonhead and pointed.

    1. Stem Cells and Regenerative Medicine

    GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells

    Rafael Jesus Fernandez III et al.
    Research Article

    Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human iPSC-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured DC mutant iAT2 cells accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC related pathologies.