Netrin-1/DCC-mediated PLC gamma 1 activation is required for axon guidance and brain structure development
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- Netrin-1/DCC-mediated PLC gamma 1 activation is required for axon guidance and brain structure development
- Kang, Du-Seock; Yang, Yong Ryoul; Lee, Cheol; Park, BumWoo; Park, Kwang Il; Seo, Jeong Kon; Seo, Young Kyo; Cho, Hyungjoon; Lucio, Cocco; Suh, Pann-Ghill
- Issue Date
- EMBO REPORTS, v.19, no.11, pp.1 - 11
- Coordinated expression of guidance molecules and their signal transduction are critical for correct brain wiring. Previous studies have shown that phospholipase C gamma1 (PLC gamma 1), 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 gamma 1 signaling and the exact role PLC gamma 1 plays in nervous system development. Here, we demonstrate that PLC gamma 1 mediates axonal guidance through a netrin-1/deleted in colorectal cancer (DCC) complex. Netrin-1/DCC activates PLC gamma 1 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 gamma 1 plays an important role in the correct development of white matter structure by mediating netrin-1/DCC signaling.
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