PUBLICATION

nev (cyfip2) Is required for retinal lamination and axon guidance in the zebrafish retinotectal system

Authors

Pittman, A.J., Gaynes, J.A., and Chien, C.B.

ID

ZDB-PUB-100614-35

Date

2010

Source

Developmental Biology 344(2): 784-794 (Journal)

Registered Authors

Chien, Chi-Bin, Gaynes, John, Pittman, Andrew

Keywords

Axon pathfinding, Retinal development, Retinotectal topography, CYFIP2/PIR121, WAVE, FMRP

MeSH Terms

Axons/metabolism
Axons/physiology*
Cell Movement/genetics
Neurogenesis
Mutation
Animals
Retinal Ganglion Cells/metabolism
Retinal Ganglion Cells/physiology
Zebrafish/genetics*
Zebrafish/physiology*
Visual Pathways/metabolism
Optic Lobe, Nonmammalian/metabolism*
Retina/metabolism

(all 13)

PubMed

20537992 Full text @ Dev. Biol.

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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cyfip2	WT	standard conditions	Long-pec	brain	ISH	Fig. 4
cyfip2	WT	standard conditions	Protruding-mouth	brain	ISH	Fig. 4
cyfip2	WT	standard conditions	Prim-5	central nervous system	ISH	Fig. 4
cyfip2	WT	standard conditions	14-19 somites	central nervous system	ISH	Fig. 4
cyfip2	WT	standard conditions	Long-pec	retina	ISH	Fig. 4
cyfip2	WT	standard conditions	Protruding-mouth	retinal ganglion cell layer	ISH	Fig. 4
cyfip2	WT	standard conditions	Protruding-mouth	retinal inner nuclear layer	ISH	Fig. 4
cyfip2	WT	standard conditions	Protruding-mouth	retinal inner plexiform layer	ISH	Fig. 4
cyfip2	WT	standard conditions	2-cell	whole organism	ISH	Fig. 4
GFP	cyfip2^{tr230b/tr230b}; zc7Tg	standard conditions	Day 5	retinal ganglion cell	IHC	Fig. 6

1 - 10 of 13

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-cyfip2	standard conditions	Protruding-mouth	retinal ganglion cell axon guidance process quality, abnormal	Fig. 3
cyfip2^{tr230b/tr230b}	standard conditions	Long-pec	retina dorsal-ventral polarity, normal	Fig. S2
cyfip2^{tr230b/tr230b}	standard conditions	Protruding-mouth	retinal ganglion cell axon guidance process quality, abnormal	Fig. 1
cyfip2^{tr230b/tr230b}	standard conditions	Day 5	retinal ganglion cell axon guidance process quality, abnormal	Fig. 8
cyfip2^{tr230b/tr230b}	standard conditions	Day 5	retinal ganglion cell axon guidance process quality, abnormal	Fig. 2
cyfip2^{tr230b/tr230b}	standard conditions	Day 5	retinal ganglion cell axon guidance process quality, abnormal	Fig. 1
cyfip2^{tr230b/tr230b}; zc7Tg	standard conditions	Day 5	amacrine cell mislocalised, abnormal	Fig. 6
cyfip2^{tr230b/tr230b}; zc7Tg	standard conditions	Day 5	retina layer formation process quality, abnormal	Fig. 6
cyfip2^{tr230b/tr230b}; zc7Tg	standard conditions	Day 5	retinal ganglion cell mislocalised, abnormal	Fig. 6

1 - 9 of 9

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ta229f		Point Mutation	cyfip2
tr230b		Point Mutation	cyfip2
zc7Tg	Tg(-17.6isl2b:GFP)	Transgenic Insertion
zc23Tg	Tg(-17.6isl2b:mCherry-HsHRAS)	Transgenic Insertion
zc25Tg	Tg(-17.6isl2b:mCherry-HsHRAS)	Transgenic Insertion

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cyfip2	MO1-cyfip2	MRPHLNO

Fish

Fish
cyfip2^{ta229f/ta229f}
cyfip2^{tr230b/tr230b}
cyfip2^{tr230b/tr230b}; zc7Tg
WT
WT + MO1-cyfip2
zc7Tg
zc23Tg
zc25Tg

Antibodies

Orthology

Gene	Orthology
cyfip2

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP
mCherry	EFG	mCherry

Mapping

Entity Type	Entity Symbol	Location
Feature	ta229f	Chr: 14 Details
Feature	tr230b	Chr: 14 Details
GENE	cyfip2	Chr: 14 Details

Pittman et al., 2010 ZDB-PUB-100614-35 PMID:20537992

nev (cyfip2) Is required for retinal lamination and axon guidance in the zebrafish retinotectal system

Pittman et al., 2010

ZDB-PUB-100614-35
PMID:20537992