Distinct functions of -Spectrin and -Spectrin during axonal pathfinding

Cell-shape changes during development require a precise coupling of the cytoskeleton with proteins situated in the plasma membrane. Important elements controlling the shape of cells are the Spectrin proteins that are expressed as a subcortical cytoskeletal meshwork linking specific membrane receptors with F-actin fibers. Here, we demonstrate that Drosophila karussell mutations affect -spectrin and lead to distinct axonal patterning defects in the embryonic CNS. karussell mutants display a slit-sensitive axonal phenotype characterized by axonal looping in stage-13 embryos. Further analyses of individual, labeled neuroblast lineages revealed abnormally structured growth cones in these animals. Cell-type-specific rescue experiments demonstrate that -Spectrin is required autonomously and non-autonomously in cortical neurons to allow normal axonal patterning. Within the cell, -Spectrin is associated with -Spectrin. We show that expression of the two genes is tightly regulated by post-translational mechanisms. Loss of -Spectrin significantly reduces levels of neuronal -Spectrin expression, whereas gain of -Spectrin leads to an increase in -Spectrin protein expression. Because the loss of -spectrin does not result in an embryonic nervous system phenotype, -Spectrin appears to act at least partially independent of -Spectrin to control axonal patterning.