Distinct functions of alpha-Spectrin and beta-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 beta-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 beta-Spectrin is required autonomously and non-autonomously in cortical neurons to allow normal axonal patterning. Within the cell, beta-Spectrin is associated with alpha-Spectrin. We show that expression of the two genes is tightly regulated by post-translational mechanisms. Loss of beta-Spectrin significantly reduces levels of neuronal alpha-Spectrin expression, whereas gain of beta-Spectrin leads to an increase in alpha-Spectrin protein expression. Because the loss of alpha-spectrin does not result in an embryonic nervous system phenotype, beta-Spectrin appears to act at least partially independent of alpha-Spectrin to control axonal patterning.
Hülsmeier
Jörn
J
Institut für Neurobiologie, Badestr. 9, 48149 Münster, Germany.
Pielage
Jan
J
Rickert
Christof
C
Technau
Gerd M
GM
Klämbt
Christian
C
Stork
Tobias
T
D000818:Animals; D001369:Axons / Q000502:physiology*; D019521:Body Patterning; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology*; D004330:Drosophila / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D020033:Protein Isoforms; D013049:Spectrin / Q000235:genetics / Q000502:physiology*
D020033:Protein Isoforms; D013049:Spectrin