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Netrin‐1/ DCC ‐mediated PLC γ1 activation is required for axon guidance and brain structure development
Author(s) -
Kang DuSeock,
Yang Yong Ryoul,
Lee Cheol,
Park BumWoo,
Park Kwang IL,
Seo Jeong Kon,
Seo Young Kyo,
Cho HyungJoon,
Cocco Lucio,
Suh PannGhill
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846250
Subject(s) - library science , computer science
Coordinated expression of guidance molecules and their signal transduction are critical for correct brain wiring. Previous studies have shown that phospholipase C gamma1 ( PLC γ1), 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 PLC γ1 signaling and the exact role PLC γ1 plays in nervous system development. Here, we demonstrate that PLC γ1 mediates axonal guidance through a netrin‐1/deleted in colorectal cancer ( DCC ) complex. Netrin‐1/ DCC activates PLC γ1 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 PLC γ1 plays an important role in the correct development of white matter structure by mediating netrin‐1/ DCC signaling.