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Abstract
In the zebrafish retinotectal system, retinal ganglion cells (RGCs) project topographically
along anterior-posterior (A-P) and dorsal-ventral (D-V) axes to innervate their primary
target, the optic tectum. In the nevermind (nev) mutant, D-V positional information
is not maintained by dorsonasal retinal axons as they project through the optic tract
to the tectum. Here we present a detailed phenotypic analysis of the retinotectal
projection in nev and show that dorsonasal axons do eventually find their correct
location on the tectum, albeit after taking a circuitous path. Interestingly, nev
seems to be specifically required for retinal axons but not for several non-retinal
axon tracts. In addition, we find that nev is required both cell autonomously and
cell nonautonomously for proper lamination of the retina. We show that nev encodes
Cyfip2 (Cytoplasmic FMRP interacting protein 2) and is thus the first known mutation
in a vertebrate Cyfip family member. Finally, we show that CYFIP2 acts cell autonomously
in the D-V sorting of dorsonasal RGC axons in the optic tract. CYFIP2 is a highly
conserved protein that lacks known domains or structural motifs but has been shown
to interact with Rac and the fragile-X mental retardation protein, suggesting intriguing
links to cytoskeletal dynamics and RNA regulation.
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