Identification of raw as a regulator of glial development

PLoS One. 2018 May 29;13(5):e0198161. doi: 10.1371/journal.pone.0198161. eCollection 2018.

Abstract

Glial cells perform numerous functions to support neuron development and function, including axon wrapping, formation of the blood brain barrier, and enhancement of synaptic transmission. We have identified a novel gene, raw, which functions in glia of the central and peripheral nervous systems in Drosophila. Reducing Raw levels in glia results in morphological defects in the brain and ventral nerve cord, as well as defects in neuron function, as revealed by decreased locomotion in crawling assays. Examination of the number of glia along peripheral nerves reveals a reduction in glial number upon raw knockdown. The reduced number of glia along peripheral nerves occurs as a result of decreased glial proliferation. As Raw has been shown to negatively regulate Jun N-terminal kinase (JNK) signaling in other developmental contexts, we examined the expression of a JNK reporter and the downstream JNK target, matrix metalloproteinase 1 (mmp1), and found that raw knockdown results in increased reporter activity and Mmp1 levels. These results are consistent with previous studies showing increased Mmp levels lead to nerve cord defects similar to those observed upon raw knockdown. In addition, knockdown of puckered, a negative feedback regulator of JNK signaling, also causes a decrease in glial number. Thus, our studies have resulted in the identification of a new regulator of gliogenesis, and demonstrate that increased JNK signaling negatively impacts glial development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Death / genetics
  • Cell Proliferation / genetics
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Knockdown Techniques
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Locomotion / genetics
  • Neuroglia / cytology*
  • Neuroglia / metabolism
  • Peripheral Nerves / cytology
  • Signal Transduction / genetics

Substances

  • Cytoskeletal Proteins
  • Drosophila Proteins
  • raw protein, Drosophila
  • JNK Mitogen-Activated Protein Kinases

Grants and funding

DL LP and JCJ were recipients of funding from Loyola University Chicago to support this research. The funder has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.