title: Dynamic expression of axon guidance cues required for optic tract development is controlled by fibroblast growth factor signaling.
abstract: Axons are guided to their targets by molecular cues expressed in their environment. How is the presence of these cues regulated? Although some evidence indicates that morphogens establish guidance cue expression as part of their role in patterning tissues, an important question is whether morphogens are then required to maintain guidance signals. We found that fibroblast growth factor (FGF) signaling sustains the expression of two guidance cues, semaphorin3A (xsema3A) and slit1 (xslit1), throughout the period of Xenopus optic tract development. With FGF receptor inhibition, xsema3A and xslit1 levels were rapidly diminished, and retinal ganglion cell axons arrested in the mid-diencephalon, before reaching their target. Importantly, direct downregulation of XSema3A and XSlit1 mostly phenocopied this axon guidance defect. Thus, FGFs promote continued presence of specific guidance cues critical for normal optic tract development, suggesting a second later role for morphogens, independent of tissue patterning, in maintaining select cues by acting to regulate their transcription.
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada. atkinsok@ucalgary.ca
authors.forename: Karen
authors.initials: K
authors.lastname: Atkinson-Leadbeater
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Bertolesi
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Hehr
authors.forename: Christine A
authors.initials: CA
authors.lastname: Webber
authors.forename: Paula B
authors.initials: PB
authors.lastname: Cechmanek
authors.forename: Sarah
authors.initials: S
authors.lastname: McFarlane
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D004027:Diencephalon / Q000166:cytology / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014795:Visual Pathways / Q000033:anatomy & histology* / Q000196:embryology / Q000378:metabolism; D014981:Xenopus
chemical_list: D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D040121:Semaphorin-3A; D005346:Fibroblast Growth Factors