RRC ID 57145
Author Arbeille E, Bashaw GJ.
Title Brain Tumor promotes axon growth across the midline through interactions with the microtubule stabilizing protein Apc2.
Journal PLoS Genet
Abstract Commissural axons must cross the midline to establish reciprocal connections between the two sides of the body. This process is highly conserved between invertebrates and vertebrates and depends on guidance cues and their receptors to instruct axon trajectories. The DCC family receptor Frazzled (Fra) signals chemoattraction and promotes midline crossing in response to its ligand Netrin. However, in Netrin or fra mutants, the loss of crossing is incomplete, suggesting the existence of additional pathways. Here, we identify Brain Tumor (Brat), a tripartite motif protein, as a new regulator of midline crossing in the Drosophila CNS. Genetic analysis indicates that Brat acts independently of the Netrin/Fra pathway. In addition, we show that through its B-Box domains, Brat acts cell autonomously to regulate the expression and localization of Adenomatous polyposis coli-2 (Apc2), a key component of the Wnt canonical signaling pathway, to promote axon growth across the midline. Genetic evidence indicates that the role of Brat and Apc2 to promote axon growth across the midline is independent of Wnt and Beta-catenin-mediated transcriptional regulation. Instead, we propose that Brat promotes midline crossing through directing the localization or stability of Apc2 at the plus ends of microtubules in navigating commissural axons. These findings define a new mechanism in the coordination of axon growth and guidance at the midline.
Volume 14(4)
Pages e1007314
Published 2018-4-1
DOI 10.1371/journal.pgen.1007314
PMID 29617376
PMC PMC5902039
MeSH Animals Animals, Genetically Modified Axons / metabolism* Central Nervous System / embryology Central Nervous System / metabolism Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / embryology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Embryo, Nonmammalian / embryology Embryo, Nonmammalian / metabolism Gene Expression Regulation, Developmental In Situ Hybridization, Fluorescence Microtubules / metabolism Netrin Receptors / genetics Netrin Receptors / metabolism Protein Binding Signal Transduction / genetics
IF 5.224
Times Cited 3