Wnt and cell polarity signaling in axon guidance

【摘要】：正The Wnt family of proteins are conserved axon guidance cues that control the pathfinding of axons along the anterior-posterior axis(A-P) axis.We showed that Wnt-Frizzled signaling is required for anterior turning spinal cord commissural axons towards the brain after then have crossed the midline.Planar cell polarity signaling conveys tissue polarity in many epithelia and is a candidate Wnt signaling pathway.To determine if the PCP pathway is involved in commissural axon guidance we examined the expression of core components of PCP signaling pathway in murine spinal cord at E11.5,a time when commissural axons turn anteriorly towards the brain after having crossing the midline of spinal cord.We found by in situ hybridization studies that Celsr3,Vangl 1,Vangl2,Frizzled3 and Prickled2 are expressed in the spinal cord.In addition,we determined by immunohistochemistry that PCP receptors Frizzled3,Celsr3 and Vangl2 are expressed on commissural axons.Furthermore,we have characterized mice with null mutation of Celsr3 and Vangl2 mutant mouse line,Looptail,for defects in commissural axon guidance.By DiI injection into E11.5 dorsal spinal cords,we observed significant randomization after midline crossing for both mouse lines implicating a loss of A-P polarity after midline crossing,phenocopying Frizzled 3 mutants.These observations suggest the involvement of the PCP pathway in the Wnt-mediated A-P guidance of commissural axons.