PUBLICATION

Polarity and morphogenesis of the eye epithelium requires the adhesion junction associated adaptor protein Traf4

Authors: Hehr, C.L., Halabi, R., McFarlane, S.
ID: ZDB-PUB-180703-2
Date: 2018
Source: Cell adhesion & migration 12(5): 489-502 (Journal)
Registered Authors: Halabi, Rami, Hehr, Carrie, McFarlane, Sarah
Keywords: Tumour necrosis factor receptor-associated factor 4, adherens junction, apico-basal polarity, evagination, eye vesicle, zebrafish
MeSH Terms: none
PubMed: 29961393 Full text @ Cell Adh. Migr.

Abstract

During development, neuroepithelial progenitors acquire apico-basal polarity and adhere to one another via apically located tight and adherens junction complexes. This polarized neuroepithelium must continue to integrate cells arising through cell divisions and intercalation, and allow for cell movements, at the same time as undergoing morphogenesis. Cell proliferation, migration and intercalation all occur in the morphing embryonic eye. To understand how eye development might depend on dynamic epithelial adhesion, we investigated the function of a known regulator of junctional plasticity, Tumour necrosis factor receptor-associated factor 4 (Traf4). traf4a mRNA is expressed in the developing eye vesicle over the period of optic cup morphogenesis, and Traf4a loss leads to disrupted evagination and elongation of the eye vesicles, and aberrant organization and apico-basal polarity of the eye epithelium. We propose a model whereby Traf4a regulates apical junction plasticity in nascent eye epithelium, allowing for its polarization and morphogenesis.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
fgf8a	WT	standard conditions	10-13 somites	anterior neural rod	ISH	Fig. 3
fgf8a	WT	standard conditions	10-13 somites	midbrain hindbrain boundary neural rod	ISH	Fig. 3
fgf8a	zf460Tg + MO1-traf4a	standard conditions	10-13 somites	anterior neural rod	ISH	Fig. 3
fgf8a	zf460Tg + MO1-traf4a	standard conditions	10-13 somites	midbrain hindbrain boundary neural rod	ISH	Fig. 3
pax6a	WT	standard conditions	10-13 somites	midbrain hindbrain boundary neural rod	ISH	Fig. 3
pax6a	WT	standard conditions	10-13 somites	optic vesicle	ISH	Fig. 3
pax6a	zf460Tg + MO1-traf4a	standard conditions	10-13 somites	midbrain hindbrain boundary neural rod	ISH	Fig. 3
pax6a	zf460Tg + MO1-traf4a	standard conditions	10-13 somites	optic vesicle	ISH	Fig. 3
rx3	WT	standard conditions	10-13 somites	anterior neural rod	ISH	Fig. 3
rx3	WT	standard conditions	10-13 somites	optic stalk	ISH	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
traf4a^ca301/ca301	standard conditions	14-19 somites	head bilateral symmetry, abnormal	Fig. 5
traf4a^ca301/ca301	standard conditions	14-19 somites	optic vesicle decreased size, abnormal	Fig. 5
traf4a^ca301/ca301	standard conditions	14-19 somites	optic vesicle increased variability of size, abnormal	Fig. 5
traf4a^ca301/ca301 + MO1-traf4a	standard conditions	10-13 somites	head bilateral symmetry, abnormal	Fig. 6
traf4a^ca301/ca301 + MO1-traf4a	standard conditions	10-13 somites	optic vesicle decreased size, abnormal	Fig. 6
traf4a^ca301/ca301 + MO1-traf4a	standard conditions	10-13 somites	optic vesicle increased variability of size, abnormal	Fig. 6
traf4a^ca301/ca301 + MO1-traf4a	standard conditions	14-19 somites	eye apoptotic process increased occurrence, abnormal	Fig. 6
traf4a^ca301/ca301; zf460Tg	standard conditions	5-9 somites to 14-19 somites	optic cup morphogenesis involved in camera-type eye development disrupted, abnormal	Fig. 8
traf4a^ca301/ca301; zf460Tg	standard conditions	5-9 somites to 14-19 somites	optic vesicle elongation disrupted, abnormal	Fig. 8
traf4a^ca301/ca301; zf460Tg	standard conditions	10-13 somites	epithelium adherens junction organization disrupted, abnormal	Fig. 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ca301		Small Deletion	traf4a
zf460Tg	Tg(Ola.Rx3:GFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
tp53	MO4-tp53	MRPHLNO
traf4a	CRISPR1-traf4a	CRISPR
traf4a	MO1-traf4a	MRPHLNO
traf4a	MO2-traf4a	MRPHLNO

Fish

Fish
traf4a^ca301/ca301
traf4a^ca301/ca301 + MO1-traf4a
traf4a^ca301/ca301; zf460Tg
WT
zf460Tg + MO1-traf4a
zf460Tg + MO2-traf4a

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Hehr et al., 2018 ZDB-PUB-180703-2 PMID:29961393

Polarity and morphogenesis of the eye epithelium requires the adhesion junction associated adaptor protein Traf4

Hehr et al., 2018

ZDB-PUB-180703-2
PMID:29961393