title: Pathfinding in a large vertebrate axon tract: isotypic interactions guide retinotectal axons at multiple choice points.
abstract: Navigating axons respond to environmental guidance signals, but can also follow axons that have gone before--pioneer axons. Pioneers have been studied extensively in simple systems, but the role of axon-axon interactions remains largely unexplored in large vertebrate axon tracts, where cohorts of identical axons could potentially use isotypic interactions to guide each other through multiple choice points. Furthermore, the relative importance of axon-axon interactions compared with axon-autonomous receptor function has not been assessed. Here, we test the role of axon-axon interactions in retinotectal development, by devising a technique to selectively remove or replace early-born retinal ganglion cells (RGCs). We find that early RGCs are both necessary and sufficient for later axons to exit the eye. Furthermore, introducing misrouted axons by transplantation reveals that guidance from eye to tectum relies heavily on interactions between axons, including both pioneer-follower and community effects. We conclude that axon-axon interactions and ligand-receptor signaling have co-equal roles, cooperating to ensure the fidelity of axon guidance in developing vertebrate tracts.
authors.affiliation: Program in Neuroscience, University of Utah Medical Center, 20 North 1900 East, Salt Lake City, UT 84132, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pittman
authors.forename: Mei-Yee
authors.initials: MY
authors.lastname: Law
authors.forename: Chi-Bin
authors.initials: CB
authors.lastname: Chien
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009900:Optic Nerve / Q000166:cytology / Q000187:drug effects; D012160:Retina / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000172:deficiency
chemical_list: D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; C413414:atoh7 protein, zebrafish