title: Coupling of NF-protocadherin signaling to axon guidance by cue-induced translation.
abstract: Cell adhesion molecules and diffusible cues both regulate axon pathfinding, yet how these two modes of signaling interact is poorly understood. The homophilic cell adhesion molecule NF-protocadherin (NFPC) is expressed in the mid-dorsal optic tract neuroepithelium and in the axons of developing retinal ganglion cells (RGC) in Xenopus laevis. Here we report that targeted disruption of NFPC function in RGC axons or the optic tract neuroepithelium results in unexpectedly localized pathfinding defects at the caudal turn in the mid-optic tract. Semaphorin 3A (Sema3A), which lies adjacent to this turn, stimulates rapid, protein synthesis-dependent increases in growth cone NFPC and its cofactor, TAF1, in vitro. In vivo, growth cones exhibit marked increases in NFPC translation reporter activity in this mid-optic tract region that are attenuated by blocking neuropilin-1 function. Our results suggest that translation-linked coupling between regionally localized diffusible cues and cell adhesion can help axons navigate discrete segments of the pathway.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Louis C
authors.initials: LC
authors.lastname: Leung
authors.forename: Vasja
authors.initials: V
authors.lastname: Urbančič
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Baudet
authors.forename: Asha
authors.initials: A
authors.lastname: Dwivedy
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Bayley
authors.forename: Aih Cheun
authors.initials: AC
authors.lastname: Lee
authors.forename: William A
authors.initials: WA
authors.lastname: Harris
authors.forename: Christine E
authors.initials: CE
authors.lastname: Holt
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002522:Chlorocebus aethiops; D003463:Cues; D018274:Electroporation; D004625:Embryo, Nonmammalian; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D046569:Neuroepithelial Cells / Q000502:physiology; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D000091363:Protocadherins; D012160:Retina / Q000166:cytology; D012165:Retinal Ganglion Cells / Q000166:cytology*; D040121:Semaphorin-3A / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014795:Visual Pathways / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D015820:Cadherins; C112030:PCDH7 protein, Xenopus; D011500:Protein Synthesis Inhibitors; D000091363:Protocadherins; D040121:Semaphorin-3A; D014157:Transcription Factors; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins; D000841:Anisomycin