title: DSCAM promotes axon fasciculation and growth in the developing optic pathway.
abstract: Although many aspects of optic pathway development are beginning to be understood, the mechanisms promoting the growth of retinal ganglion cell (RGC) axons toward visual targets remain largely unknown. Down syndrome cell adhesion molecule (Dscam) is expressed by mouse RGCs shortly after they differentiate at embryonic day 12 and is essential for multiple aspects of postnatal visual system development. Here we show thatDscamis also required during embryonic development for the fasciculation and growth of RGC axons.Dscamis expressed along the developing optic pathway in a pattern consistent with a role in regulating RGC axon outgrowth. In mice carrying spontaneous mutations inDscam(Dscamdel17;Dscam2J), RGC axons pathfind normally, but growth from the chiasm toward their targets is impaired, resulting in a delay in RGC axons reaching the dorsal thalamus compared with that seen in wild-type littermates. Conversely,Dscamgain of function results in exuberant growth into the dorsal thalamus. The growth of ipsilaterally projecting axons is particularly affected. Axon organization in the optic chiasm and tract and RGC growth cone morphologies are also altered inDscammutants. In vitro DSCAM promotes RGC axon growth and fasciculation, and can act independently of cell contact. In vitro and in situ DSCAM is required both in the RGC axons and in their environment for the promotion of axon outgrowth, consistent with a homotypic mode of action. These findings identify DSCAM as a permissive signal that promotes the growth and fasciculation of RGC axons, controlling the timing of when RGC axons reach their targets.
authors.affiliation: School of Medicine, Medical Sciences, and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Freyja M
authors.initials: FM
authors.lastname: Bruce
authors.affiliation: School of Medicine, Medical Sciences, and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Samantha
authors.initials: S
authors.lastname: Brown
authors.affiliation: School of Medicine, Medical Sciences, and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Smith
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID 83844; fuerst@uidaho.edu l.erskine@abdn.ac.uk.|Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) Medical Education Program, University of Idaho, Moscow, ID 83844.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Fuerst
authors.affiliation: School of Medicine, Medical Sciences, and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; fuerst@uidaho.edu l.erskine@abdn.ac.uk.
authors.forename: Lynda
authors.initials: L
authors.lastname: Erskine
mesh_terms: D000818:Animals; D000071448:Axon Fasciculation / Q000235:genetics*; D001369:Axons / Q000378:metabolism; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009897:Optic Chiasm / Q000196:embryology / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D014795:Visual Pathways / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C491735:Dscam protein, mouse
keywords: axon guidance; development; growth cone; optic chiasm; visual system