Targeted disruption of Ca(2+)-calmodulin signaling in Drosophila growth cones leads to stalls in axon extension and errors in axon guidance.

Abstract

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.