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
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  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
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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.

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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

Version 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.

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  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

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Further reading

    1. Developmental Biology
    2. Neuroscience

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

    Yonggang Xie, Xiaosu Li ... Sijun Zhu
    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
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    Neuroblasts: Maintaining neural stem cell identity in the brain

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    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.

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