Skip to main content

Advertisement

SpringerLink
Log in

Understanding how differentiation is maintained: lessons from the Drosophila brain

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The ability to maintain cells in a differentiated state and to prevent them from reprogramming into a multipotent state has recently emerged as a central theme in neural development as well as in oncogenesis. In the developing central nervous system (CNS) of the fruit fly Drosophila, several transcription factors were recently identified to be required in postmitotic cells to maintain differentiation, and in their absence, mature neurons undergo dedifferentiation, giving rise to proliferative neural stem cells and ultimately to tumor growth. In this review, we will highlight the current understanding of dedifferentiation and cell plasticity in the Drosophila CNS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Gurdon JB (1962) Adult frogs derived from the nuclei of single somatic cells. Dev Biol 4:256–273

    Article  CAS  PubMed  Google Scholar 

  2. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  3. Friedmann-Morvinski D, Verma IM (2014) Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO Rep 15:244–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Brand AH, Livesey FJ (2011) Neural stem cell biology in vertebrates and invertebrates: more alike than different? Neuron 70:719–729

    Article  CAS  PubMed  Google Scholar 

  5. Homem CCF, Knoblich JA (2012) Drosophila neuroblasts: a model for stem cell biology. Development 139:4297–4310

    Article  CAS  PubMed  Google Scholar 

  6. Choksi SP et al (2006) Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev Cell 11:775–789

    Article  CAS  PubMed  Google Scholar 

  7. Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37:1125–1129

    Article  CAS  PubMed  Google Scholar 

  8. Bello B, Reichert H, Hirth F (2006) The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development. 133:2639–2648

    Article  CAS  PubMed  Google Scholar 

  9. Betschinger J, Mechtler K, Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124:1241–1253

    Article  CAS  PubMed  Google Scholar 

  10. Lee C-Y, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ (2006) Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell 10:441–449

    Article  CAS  PubMed  Google Scholar 

  11. Wang H et al (2006) Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev 20:3453–3463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bowman SK et al (2008) The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell 14:535–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lin S et al (2009) Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain. Development 137:43–51

    Article  Google Scholar 

  14. Weng M, Golden KL, Lee C-Y (2010) dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila. Dev Cell 18:126–135

    Article  CAS  PubMed  Google Scholar 

  15. San-Juán BP, Baonza A (2011) The bHLH factor deadpan is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila. Dev Biol 352:70–82

    Article  PubMed  Google Scholar 

  16. Song Y, Lu B (2011) Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila. Genes Dev 25:2644–2658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Xiao Q, Komori H, Lee C-Y (2012) klumpfuss distinguishes stem cells from progenitor cells during asymmetric neuroblast division. Development 139:2670–2680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zacharioudaki E, Magadi SS, Delidakis C (2012) bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation. Development 139:1258–1269

    Article  CAS  PubMed  Google Scholar 

  19. Froldi F et al (2015) The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells. Genes Dev 29:129–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Carney TD, Struck AJ, Doe CQ (2013) midlife crisis encodes a conserved zinc-finger protein required to maintain neuronal differentiation in Drosophila. Development 140:4155–4164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Southall TD, Davidson CM, Miller C, Carr A, Brand AH (2014) Dedifferentiation of neurons precedes tumor formation in Lola mutants. Dev Cell 28:685–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Oliver G et al (1993) Prox 1, a prospero-related homeobox gene expressed during mouse development. Mech Dev 44:3–16

    Article  CAS  PubMed  Google Scholar 

  23. Zinovieva RD et al (1996) Structure and chromosomal localization of the human homeobox gene Prox 1. Genomics 35:517–522

    Article  CAS  PubMed  Google Scholar 

  24. Elsir T, Smits A, Lindström MS, Nistér M (2012) Transcription factor PROX1: its role in development and cancer. Cancer Metastasis Rev 31:793–805

    Article  CAS  PubMed  Google Scholar 

  25. Misra K, Mishra K, Gui H, Matise MP (2008) Prox1 regulates a transitory state for interneuron neurogenesis in the spinal cord. Dev Dyn 237:393–402

    Article  PubMed  Google Scholar 

  26. Elkouris M et al (2011) Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis. Stem Cells 29:89–98

    Article  CAS  PubMed  Google Scholar 

  27. Kaltezioti V et al (2010) Prox1 regulates the notch1-mediated inhibition of neurogenesis. PLoS Biol 8:e1000565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Karalay O, Jessberger S (2011) Translating niche-derived signals into neurogenesis: the function of Prox1 in the adult hippocampus. Cell Cycle 10:2239–2240

    Article  CAS  PubMed  Google Scholar 

  29. Stergiopoulos A, Elkouris M, Politis PK (2014) Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification. Front Cell Neurosci 8:454

    PubMed  PubMed Central  Google Scholar 

  30. Wu J (2001) Inhibition of touch cell fate by egl-44 and egl-46 in C. elegans. Genes Dev 15:789–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Candal E et al (2007) Ol-insm1b, a SNAG family transcription factor involved in cell cycle arrest during medaka development. Dev Biol 309:1–17

    Article  CAS  PubMed  Google Scholar 

  32. Forbes-Osborne MA, Wilson SG, Morris AC (2013) Developmental biology. Dev Biol 380:157–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Farkas LM et al (2008) Insulinoma-associated 1 has a panneurogenic role and promotes the generation and expansion of basal progenitors in the developing mouse neocortex. Neuron 60:40–55

    Article  CAS  PubMed  Google Scholar 

  34. Jia S et al (2015) Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function. EMBO J 34:1417–1433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Breslin MB, Zhu M, Lan MS (2003) NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system. J Biol Chem 278:38991–38997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fuller GN, Scheithauer BW (2007) The 2007 revised World Health Organization (WHO) classification of tumours of the central nervous system: newly codified entities. Brain Pathol 17:304–307

    Article  PubMed  Google Scholar 

  37. Friedmann-Morvinski D et al (2012) Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 338:1080–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bachoo RM et al (2002) Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1:269–277

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Joep Vissers for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. Peter MacCallum Cancer Centre, East Melbourne, VIC, 3002, Australia

    Francesca Froldi & Louise Y. Cheng

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3010, Australia

    Francesca Froldi & Louise Y. Cheng

Authors
  1. Francesca Froldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Louise Y. Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Louise Y. Cheng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Froldi, F., Cheng, L.Y. Understanding how differentiation is maintained: lessons from the Drosophila brain. Cell. Mol. Life Sci. 73, 1641–1644 (2016). https://doi.org/10.1007/s00018-016-2144-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-016-2144-y

Keywords

Search

Navigation