TY - JOUR
T1 - Differential functions of the C. elegans FGF receptor in axon outgrowth and maintenance of axon position
AU - Bülow, Hannes E.
AU - Boulin, Thomas
AU - Hobert, Oliver
N1 - Funding Information:
We thank David Hall and Martin Wakeland for collecting egl-15 EM data, the Caenorhabditis elegans Genetics Center and members of the worm community for providing strains and reagents, Donald Court for bacterial strains used for recombineering, Michael Stern for communicating unpublished results, and William Wadsworth, Iva Greenwald, and members of the Hobart lab for comments on the manuscript. This work was supported by grants from the NIH, McKnight Foundation, American Paralysis Association, and the Whitehall Foundation to O.H. and by a fellowship from the Boehringer Ingelheim Fonds to T.B.
PY - 2004/5/13
Y1 - 2004/5/13
N2 - Wiring of the nervous system requires that axons navigate to their targets and maintain their correct positions in axon fascicles after termination of axon outgrowth. We show here that the C. elegans fibroblast growth factor receptor (FGFR), EGL-15, affects both processes in fundamentally distinct manners. FGF-dependent activation of the EGL-15 tyrosine kinase and subsequently the GTPase LET-60/ras is required within epidermal cells, the substratum for most outgrowing axon, for appropriate outgrowth of specific axon classes to their target area. In contrast, genetic elimination of the FGFR isoform EGL-15(5A), defined by the inclusion of an alternative extracellular interimmunoglobulin domain, has no consequence for axon outgrowth but leads to a failure to postembryonically maintain axon position within defined axon fascicles. An engineered, secreted form of EGL-15(5A) containing only its ectodomain is sufficient for maintenance of axon position, thus providing novel insights into receptor tyrosine kinase function and the process of maintaining axon position.
AB - Wiring of the nervous system requires that axons navigate to their targets and maintain their correct positions in axon fascicles after termination of axon outgrowth. We show here that the C. elegans fibroblast growth factor receptor (FGFR), EGL-15, affects both processes in fundamentally distinct manners. FGF-dependent activation of the EGL-15 tyrosine kinase and subsequently the GTPase LET-60/ras is required within epidermal cells, the substratum for most outgrowing axon, for appropriate outgrowth of specific axon classes to their target area. In contrast, genetic elimination of the FGFR isoform EGL-15(5A), defined by the inclusion of an alternative extracellular interimmunoglobulin domain, has no consequence for axon outgrowth but leads to a failure to postembryonically maintain axon position within defined axon fascicles. An engineered, secreted form of EGL-15(5A) containing only its ectodomain is sufficient for maintenance of axon position, thus providing novel insights into receptor tyrosine kinase function and the process of maintaining axon position.
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U2 - 10.1016/S0896-6273(04)00246-6
DO - 10.1016/S0896-6273(04)00246-6
M3 - Article
C2 - 15134634
AN - SCOPUS:2342612634
SN - 0896-6273
VL - 42
SP - 367
EP - 374
JO - Neuron
JF - Neuron
IS - 3
ER -