Abelson tyrosine kinase and Calmodulin interact synergistically to transduce midline guidance cues in the Drosophila embryonic CNS.
Calmodulin and Abelson tyrosine kinase are key signaling molecules transducing guidance cues at the Drosophila embryonic midline. A reduction in the signaling strength of either pathway alone induces ectopic midline crossing errors in a few segments. When Calmodulin and Abelson signaling levels are simultaneously reduced, the frequency of ectopic crossovers is synergistically enhanced as all segments exhibit crossing errors. But as the level of signaling is further reduced, commissures begin to fuse and large gaps form in the longitudinal connectives. Quantitative analysis suggests that the level of Abelson activity is particularly important. Like Calmodulin, Abelson interacts with son-of-sevenless to increase ectopic crossovers suggesting all three contribute to midline repulsive signaling. Axons cross the midline in almost every segment if Frazzled is co-overexpressed with the Calmodulin inhibitor, but the crossovers induced by the Calmodulin inhibitor itself do not require endogenous Frazzled. Thus, Calmodulin and Abelson tyrosine kinase are key signaling molecules working synergistically to transduce both midline attractive and repulsive cues. While they may function downstream of specific receptors, the emergence of commissural and longitudinal connective defects point to a novel convergence of Calmodulin and Abelson signaling during the regulation of actin and myosin dynamics underlying a guidance decision.
Hsouna
Anita
A
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.
VanBerkum
Mark F A
MF
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D003463:Cues; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000201:enzymology; D047108:Embryonic Development / Q000235:genetics; D007839:Functional Laterality / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000196:embryology / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000201:enzymology* / Q000648:ultrastructure; D009218:Myosins / Q000378:metabolism; D009420:Nervous System / Q000196:embryology* / Q000201:enzymology; D000075386:Netrin Receptors; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D020839:Son of Sevenless Protein, Drosophila / Q000235:genetics / Q000378:metabolism
D002147:Calmodulin; D029721:Drosophila Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D020839:Son of Sevenless Protein, Drosophila; C000617310:fra protein, Drosophila; D011505:Protein-Tyrosine Kinases; C506548:Abl protein, Drosophila; D009218:Myosins