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Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve ring placement in C. elegans
Jason R. Kennerdell, Richard D. Fetter, Cornelia I. Bargmann


Wnt signaling through Frizzled proteins guides posterior cells and axons in C. elegans into different spatial domains. Here we demonstrate an essential role for Wnt signaling through Ror tyrosine kinase homologs in the most prominent anterior neuropil, the nerve ring. A genetic screen uncovered cwn-2, the C. elegans homolog of Wnt5, as a regulator of nerve ring placement. In cwn-2 mutants, all neuronal structures in and around the nerve ring are shifted to an abnormal anterior position. cwn-2 is required at the time of nerve ring formation; it is expressed by cells posterior of the nerve ring, but its precise site of expression is not critical for its function. In nerve ring development, cwn-2 acts primarily through the Wnt receptor CAM-1 (Ror), together with the Frizzled protein MIG-1, with parallel roles for the Frizzled protein CFZ-2. The identification of CAM-1 as a CWN-2 receptor contrasts with CAM-1 action as a non-receptor in other C. elegans Wnt pathways. Cell-specific rescue of cam-1 and cell ablation experiments reveal a crucial role for the SIA and SIB neurons in positioning the nerve ring, linking Wnt signaling to specific cells that organize the anterior nervous system.


  • We thank Michael Francis, Massimo Hilliard, Tinya Fleming, Gian Garriga, the C. elegans Gene Knockout Consortium, the Sanger Institute and Yuji Kohara for strains and reagents; and Massimo Hilliard, Tapan Maniar, Jennifer Garrison, Sreekanth Chalasani and Yasunori Saheki for comments on the manuscript. This work was supported by HHMI. J.R.K. was supported by an HHMI Predoctoral Fellowship and C.I.B. is an Investigator of HHMI. Deposited in PMC for release after 6 months.

    • Accepted September 16, 2009.
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