Altered levels of Gq activity modulate axonal pathfinding in Drosophila.
A majority of neurons that form the ventral nerve cord send out long axons that cross the midline through anterior or posterior commissures. A smaller fraction extend longitudinally and never cross the midline. The decision to cross the midline is governed by a balance of attractive and repulsive signals. We have explored the role of a G-protein, Galphaq, in altering this balance in Drosophila. A splice variant of Galphaq, dgqalpha3, is expressed in early axonal growth cones, which go to form the commissures in the Drosophila embryonic CNS. Misexpression of a gain-of-function transgene of dgqalpha3 (AcGq3) leads to ectopic midline crossing. Analysis of the AcGq3 phenotype in roundabout and frazzled mutants shows that AcGq3 function is antagonistic to Robo signaling and requires Frazzled to promote ectopic midline crossing. Our results show for the first time that a heterotrimeric G-protein can affect the balance of attractive versus repulsive cues in the growth cone and that it can function as a component of signaling pathways that regulate axonal pathfinding.
Ratnaparkhi
Anuradha
A
National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
Banerjee
Santanu
S
Hasan
Gaiti
G
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D017930:Genes, Reporter; D020439:Growth Cones / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019076:Transgenes; D000097905:Roundabout Proteins
D029721:Drosophila Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C000617310:fra protein, Drosophila