[Abstract Title]. - Society for Neuroscience

Topic: A.04.i. Dendritic growth and branching
Support: NIH Grant EY016031
Title: DSCAMs in the development of the mouse retina
Authors: *R. W. BURGESS 1 , P. G. FUERST 2 , F. BRUCE 3 , A. KOIZUMI 4 , L. ERSKINE 3 , R.
H. MASLAND 5 ;
1 Res., The Jackson Lab., Bar Harbor, ME; 2 Jackson Lab., Bar Harbor, ME; 3 Inst. of Med. Sci.,
Univ. of Aberdeen, Aberdeen, United Kingdom; 4 Natl. Insistute for Physiological Sci., Okazaki,
Japan; 5 Massachusetts Gen. Hosp., Boston, MA
Abstract: Retinal neurons establish their spatial domains by arborizing their processes, which
requires the self-avoidance of neurites from an individual cell, and by spacing their cell bodies,
which requires positioning the soma and establishing a zone within which other cells of the same
type are excluded. The mosaic patterns of distinct cell types form independently and can overlap.
Therefore, there must be unique identifiers for each cell type that mediate these self-recognition
and avoidance events. These molecular signals are now being identified in the vertebrate retina.
We have shown that DSCAM in the mouse retina is required for some types of retinal amacrine
cells to arborize their processes and to maintain the spacing of their cell bodies. In the mutant
retina, cells that would normally express Dscam have hyperfasciculated processes, preventing
them from creating an orderly arbor. The cell bodies of these neurons are randomly distributed or
pulled into clumps rather than being spaced in regular mosaics. Retinal ganglion cells in the
Dscam -/- mice also show a dendrite arborization phenotype, and cell bodies are abnormally
spaced even at very early ages. Most axonal projections are initially normal, but extensive axonal
remodeling occurs after eye opening. The ganglion cell expression of Dscam and the mutant
phenotype in these cells is more complicated than in amacrine cells, and suggest that Dscam may
function at multiple stages of ganglion cell development. Other retinal cell populations express
related genes that may also function as recognition molecules. Dscam-like1 is expressed in a
non-overlapping subset of amacrine cells and ON-bipolar neurons. In mice lacking Dscam-like1,
there is a disorganization in these cell populations that is preliminarily similar to the defects
observed in Dscam -/- retinas. Our results indicate that mouse DSCAMs mediate isoneuronal selfavoidance
for arborization, and heteroneuronal self-avoidance within specific cell types to
prevent fasciculation and to preserve mosaic spacing. These functions are highly analogous to
those of Drosophila Dscam and Dscam2, are necessary for establishing orderly retinal circuitry,
and suggest mammalian DSCAMs may serve similar roles in other regions of the central nervous
system.
Disclosures: R.W. Burgess, None; P.G. Fuerst, None; F. Bruce, None; A. Koizumi, None; L.
Erskine, None; R.H. Masland, None.
Poster