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Netrin‐1/DCC‐mediated PLCγ1 activation is required for axon guidance and brain structure development

View ORCID ProfileDu‐Seock Kang, Yong Ryoul Yang, Cheol Lee, BumWoo Park, Kwang IL Park, Jeong Kon Seo, Young Kyo Seo, HyungJoon Cho, Cocco Lucio, View ORCID ProfilePann‐Ghill Suh
DOI 10.15252/embr.201846250 | Published online 17.09.2018
EMBO reports (2018) e46250
Du‐Seock Kang
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, KoreaCollege of Life Science & Bioengineering, Korea Advanced Institute of Science & Technology (KAIST), Daejeon, Korea
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Yong Ryoul Yang
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
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Cheol Lee
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
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BumWoo Park
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
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Kwang IL Park
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
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Jeong Kon Seo
UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, Korea
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Young Kyo Seo
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
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HyungJoon Cho
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
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Cocco Lucio
Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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Pann‐Ghill Suh
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
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Author Affiliations

  1. Du‐Seock Kang1,2,
  2. Yong Ryoul Yang1,
  3. Cheol Lee1,
  4. BumWoo Park1,
  5. Kwang IL Park1,
  6. Jeong Kon Seo3,
  7. Young Kyo Seo1,
  8. HyungJoon Cho1,
  9. Cocco Lucio4 and
  10. Pann‐Ghill Suh (pgsuh{at}unist.ac.kr)*,1
  1. 1School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
  2. 2College of Life Science & Bioengineering, Korea Advanced Institute of Science & Technology (KAIST), Daejeon, Korea
  3. 3UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, Korea
  4. 4Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
  1. ↵*Corresponding author. Tel: +82 52 217 2621; E‐mail: pgsuh{at}unist.ac.kr
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Abstract

Coordinated expression of guidance molecules and their signal transduction are critical for correct brain wiring. Previous studies have shown that phospholipase C gamma1 (PLCγ1), a signal transducer of receptor tyrosine kinases, plays a specific role in the regulation of neuronal cell morphology and motility in vitro. However, several questions remain regarding the extracellular stimulus that triggers PLCγ1 signaling and the exact role PLCγ1 plays in nervous system development. Here, we demonstrate that PLCγ1 mediates axonal guidance through a netrin‐1/deleted in colorectal cancer (DCC) complex. Netrin‐1/DCC activates PLCγ1 through Src kinase to induce actin cytoskeleton rearrangement. Neuronal progenitor‐specific knockout of Plcg1 in mice causes axon guidance defects in the dorsal part of the mesencephalon during embryogenesis. Adult Plcg1‐deficient mice exhibit structural alterations in the corpus callosum, substantia innominata, and olfactory tubercle. These results suggest that PLCγ1 plays an important role in the correct development of white matter structure by mediating netrin‐1/DCC signaling.

Synopsis

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Netrin‐1 activates PLCγ1 via Src kinase, which is crucial for axon guidance and corpus callosum and mDA system development.

  • PLCγ1 promotes axon extension and guidance by mediating netrin‐1/DCC signaling.

  • Netrin‐1 activates the lipase activity of PLCγ1 through phosphorylation of the Y783‐residue by Src kinase.

  • Disruption of PLCγ1 signaling adversely affects corpus callosum structural and mDA system development.

  • axon guidance
  • DCC
  • mesencephalon
  • neural development
  • PLCγ1

EMBO Reports (2018) e46250

  • Received April 9, 2018.
  • Revision received August 11, 2018.
  • Accepted August 23, 2018.
  • © 2018 The Authors
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Volume 20, Issue 2
01 February 2019
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