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
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.
EMBO Reports (2018) e46250
- Received April 9, 2018.
- Revision received August 11, 2018.
- Accepted August 23, 2018.
- © 2018 The Authors
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