Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum.

TitleWnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum.
Publication TypeJournal Article
Year of Publication2012
AuthorsB Hutchins, I, Li, L, Kalil, K
JournalSci Signal
Date Published2012 Jan 10
KeywordsAxons, Calcium Signaling, Corpus Callosum, Humans, Wnt Proteins

Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP(3)) receptors and calcium entry through transient receptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest that growth and guidance of postcrossing callosal axons by Wnt-Ryk-calcium signaling involves axon repulsion through CaMKII.

Alternate JournalSci Signal
Citation Key10.1126/scisignal.2002523
PubMed ID22234611
Grant ListF31 GM080164 / GM / NIGMS NIH HHS / United States
GM801642 / GM / NIGMS NIH HHS / United States
NS14428 / NS / NINDS NIH HHS / United States