title: DSCAM promotes refinement in the mouse retina through cell death and restriction of exploring dendrites.
abstract: In this study we develop and use a gain-of-function mouse allele of the Down syndrome cell adhesion molecule (Dscam) to complement loss-of-function models. We assay the role of Dscam in promoting cell death, spacing, and laminar targeting of neurons in the developing mouse retina. We find that ectopic or overexpression of Dscam is sufficient to drive cell death. Gain-of-function studies indicate that Dscam is not sufficient to increase spatial organization, prevent cell-to-cell pairing, or promote active avoidance in the mouse retina, despite the similarity of the Dscam loss-of-function phenotype in the mouse retina to phenotypes observed in Drosophila Dscam1 mutants. Both gain- and loss-of-function studies support a role for Dscam in targeting neurites; DSCAM is necessary for precise dendrite lamination, and is sufficient to retarget neurites of outer retinal cells after ectopic expression. We further demonstrate that DSCAM guides dendrite targeting in type 2 dopaminergic amacrine cells, by restricting the stratum in which exploring retinal dendrites stabilize, in a Dscam dosage-dependent manner. Based on these results we propose a single model to account for the numerous Dscam gain- and loss-of-function phenotypes reported in the mouse retina whereby DSCAM eliminates inappropriately placed cells and connections.
authors: University of Idaho, Department of Biological Sciences, Moscow, Idaho 83844.
authors: Shuai
authors: http://orcid.org/0000-0001-5889-3655
authors: S
authors: Li
authors: University of Idaho, Department of Biological Sciences, Moscow, Idaho 83844.
authors: Joshua M
authors: JM
authors: Sukeena
authors: University of Idaho, Department of Biological Sciences, Moscow, Idaho 83844.
authors: Aaron B
authors: AB
authors: Simmons
authors: University of Idaho, Department of Biological Sciences, Moscow, Idaho 83844.
authors: Ethan J
authors: EJ
authors: Hansen
authors: University of Idaho, Department of Biological Sciences, Moscow, Idaho 83844, WWAMI Medical Education Program, Moscow, Idaho 83844.
authors: Renee E
authors: RE
authors: Nuhn
authors: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio 44106, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio 44195, and.
authors: Ivy S
authors: IS
authors: Samuels
authors: University of Idaho, Department of Biological Sciences, Moscow, Idaho 83844, WWAMI Medical Education Program, Moscow, Idaho 83844 fuerst@uidaho.edu.
authors: Peter G
authors: http://orcid.org/0000-0002-1671-0926
authors: PG
authors: Fuerst
mesh_terms: D025042:Amacrine Cells / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D004596:Electroretinography; D063928:Ependymoglial Cells / Q000502:physiology* / Q000648:ultrastructure; D005136:Eye Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009154:Mutation; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012160:Retina / Q000166:cytology*; D014795:Visual Pathways / Q000254:growth & development / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D015815:Cell Adhesion Molecules; C491735:Dscam protein, mouse; D005136:Eye Proteins; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D051028:bcl-2-Associated X Protein
keywords: ERG; apoptosis; bax; dendrite; mosaic; physiology