PUBLICATION

Lysyl hydroxylase 3 is required for normal lens capsule formation and maintenance of lens epithelium integrity and fate

Authors

Taler, K., Weiss, O., Rotem, S., Rubinstein, A.M., Seritrakul, P., Gross, J.M., Inbal, A.

ID

ZDB-PUB-191102-11

Date

2019

Source

Developmental Biology 458(2): 177-188 (Journal)

Registered Authors

Gross, Jeffrey, Inbal, Adi, Seritrakul, Pawat

Keywords

Lens capsule, Lens epithelium, Lysyl hydroxylase 3, TGFβ, Zebrafish, plod3

MeSH Terms

Embryonic Development
Lens Capsule, Crystalline/embryology*
Lens Capsule, Crystalline/metabolism*
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics*
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism
Glycosyltransferases/genetics*
Glycosyltransferases/metabolism
Cataract/genetics
Epithelial Cells/pathology
Epithelium/pathology
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism
Zebrafish
Cell Differentiation/physiology
Phenotype
Actins/genetics
Actins/metabolism
Animals
Lens, Crystalline/embryology

(all 19)

PubMed

31669351 Full text @ Dev. Biol.

Abstract

Lens abnormalities are a major cause of reduced vision and blindness. One mechanism that can lead to reduced lens transparency, i.e. cataract, is abnormal behavior of lens epithelial cells (LECs), the precursors of the transparent lens fiber cells. Here we describe a zebrafish mutation causing the embryonic lens epithelium to generate cellular masses comprising partially differentiated lens fiber cells. We identify the mutant gene as plod3, which encodes for Lysyl hydroxylase 3 (Lh3), an enzyme essential for modification of collagens, including Collagen IV, a main component of the lens capsule. We show that plod3-deficient lenses have abnormal lens epithelium from an early developmental stage, as well as abnormal lens capsules. Subsequently, upregulation of TGFβ signaling takes place, which drives the formation of lens epithelial cellular masses. We identify a similar phenotype in Collagen IVα5-deficient embryos, suggesting a key role for the defective lens capsule in the pathogenesis. We propose that plod3 and col4a5 mutant zebrafish can serve as useful models for better understanding the biology of LECs during embryonic development and in formation of lens epithelium-derived cataract.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	huj19Tg	standard conditions	Protruding-mouth	lens epithelium nucleus	IFL	Fig. 2
EGFP	plod3^vu222/vu222; huj19Tg	standard conditions	Protruding-mouth	lens epithelium nucleus	IFL	Fig. 2
EGFP	plod3^vu222/vu222; vu119Tg	standard conditions	Protruding-mouth	lens epithelium	IFL	Fig. 5
plod3	plod3^vu222/vu222	standard conditions	Long-pec	whole organism	RTPCR	Fig. 4
plod3	WT	standard conditions	Long-pec	ciliary marginal zone	ISH	Fig. 4
plod3	WT	standard conditions	Prim-15	lens epithelium	ISH	Fig. 4
plod3	WT	standard conditions	Prim-15	lens fiber cell	ISH	Fig. 4
plod3	WT	standard conditions	Long-pec	whole organism	RTPCR	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: SB 431542	Day 4	lens epithelium morphology, normal	Fig. 9
col4a5^s510/s510	standard conditions	Day 4	inner ear morphology, normal	Fig. 9
col4a5^s510/s510	standard conditions	Day 4	lens dislocated, abnormal	Fig. 9
col4a5^s510/s510	standard conditions	Day 4	lens epithelium hypertrophic, abnormal	Fig. 9
col4a5^s510/s510	standard conditions	Day 4	lens epithelium malformed, abnormal	Fig. 9
col4a5^s510/s510	standard conditions	Day 4	lens shape, abnormal	Fig. 9
col4a5^s510/s510	standard conditions	Day 4	whole organism normal length, normal	Fig. 9
col4a5^s510/s510	chemical treatment by environment: SB 431542	Day 4	lens epithelium morphology, ameliorated	Fig. 9
col4a5^s510/s510	chemical treatment by environment: SB 431542	Day 4	lens position, ameliorated	Fig. 9
plod3^tv205a/+; plod3^vu222/+	standard conditions	Protruding-mouth	inner ear bulbous, abnormal	Fig. 4

1 - 10 of 80

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
huj19Tg	Tg(foxe3:NLS-EGFP)	Transgenic Insertion
s510		Point Mutation	col4a5
tv205a		Point Mutation	plod3
vu119Tg	Tg(Ola.Actb:Hsa.HRAS-EGFP)	Transgenic Insertion
vu222		Unknown	plod3

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
col4a5^s510/s510
huj19Tg
plod3^tv205a/+; plod3^vu222/+
plod3^{tv205a/tv205a}
plod3^vu222/vu222
plod3^vu222/vu222; huj19Tg
plod3^vu222/vu222; vu119Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Taler et al., 2019 ZDB-PUB-191102-11 PMID:31669351

Lysyl hydroxylase 3 is required for normal lens capsule formation and maintenance of lens epithelium integrity and fate

Taler et al., 2019

ZDB-PUB-191102-11
PMID:31669351