Targeted disruption of Ca(2+)-calmodulin signaling in Drosophila growth cones leads to stalls in axon extension and errors in axon guidance.
Ca(2+)-calmodulin (CaM) function was selectively disrupted in a specific subset of growth cones in transgenic Drosophila embryos in which a specific enhancer element drives the expression of the kinesin motor domain fused to a CaM antagonist peptide (kinesin-antagonist or KA, which blocks CaM binding to target proteins) or CaM itself (kinesin-CaM or KC, which acts as a Ca(2+)-binding protein). In both KA and KC mutant embryos, specific growth cones exhibit dosage-dependent stalls in axon extension and errors in axon guidance, including both defects in fasciculation and abnormal crossings of the midline. These results demonstrate an in vivo function for Ca(2+)-CaM signaling in growth cone extension and guidance and suggest that Ca(2+)-CaM may in part regulate specific growth cone decisions, including when to defasciculate and whether or not to cross the midline.
VanBerkum
M F
MF
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Goodman
C S
CS
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001483:Base Sequence; D015153:Blotting, Western; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D004330:Drosophila / Q000502:physiology*; D015870:Gene Expression; D005818:Genetic Engineering; D016547:Kinesins / Q000235:genetics / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure*; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000235:genetics
D002147:Calmodulin; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase; D016547:Kinesins; D002118:Calcium