dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation

PLoS Genet. 2017 Mar 7;13(3):e1006647. doi: 10.1371/journal.pgen.1006647. eCollection 2017 Mar.

Abstract

In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-β signalling activation.

MeSH terms

  • Animals
  • Apoptosis
  • Axons / metabolism
  • Cell Differentiation / physiology
  • Cell Movement
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster
  • Extracellular Matrix / metabolism
  • Female
  • MAP Kinase Kinase 4 / metabolism
  • Male
  • Neurogenesis
  • Neuroglia / metabolism*
  • Neurons / metabolism*
  • Photoreceptor Cells, Invertebrate / metabolism*
  • Retina / cytology
  • Signal Transduction
  • Stem Cells / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta / metabolism

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Myc protein, Drosophila
  • Transcription Factors
  • Transforming Growth Factor beta
  • MAP Kinase Kinase 4

Grants and funding

This work is a result of the project Norte-01-0145-FEDER-000008 - Porto Neurosciences and Neurologic Disease Research Initiative at I3S and the project Norte-01-0145-FEDER-000029 - Advancing Cancer Research: From basic knowledge to application, both supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). LT is funded by a Fundação para a Ciência e Tecnologia Fellowship (SFRH/BPD/95336/2013). PSP is a recipient of a Portuguese "Investigator FCT" contract. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.