PUBLICATION

Uhrf1 and Dnmt1 are required for development and maintenance of the zebrafish lens

Authors

Tittle, R.K., Sze, R., Ng, A., Nuckels, R.J., Swartz, M.E., Anderson, R.M., Bosch, J., Stainier, D.Y., Eberhart, J.K., and Gross, J.M.

ID

ZDB-PUB-101209-12

Date

2011

Source

Developmental Biology 350(1): 50-63 (Journal)

Registered Authors

Anderson, Ryan, Eberhart, Johann, Gross, Jeffrey, Ng, Anthony, Nuckels, Richard, Stainier, Didier, Swartz, Mary, Sze, Ryan, Tittle, Rachel

Keywords

Zebrafish, Dnmt1, Uhrf1, Lens development, DNA methylation

MeSH Terms

Lens, Crystalline/cytology
Lens, Crystalline/embryology*
Lens, Crystalline/metabolism
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/metabolism
DNA Methylation*
Mutation
Alleles
Animals
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Retina/cytology
Retina/embryology
Retina/metabolism
Gene Expression Regulation, Developmental
Epigenesis, Genetic
Trans-Activators/genetics
Trans-Activators/metabolism*
DNA (Cytosine-5-)-Methyltransferases/genetics
DNA (Cytosine-5-)-Methyltransferases/metabolism*
Gene Expression Regulation, Plant
Apoptosis
Cell Differentiation
Epithelium/embryology
Epithelium/metabolism

(all 26)

PubMed

21126517 Full text @ Dev. Biol.

Abstract

DNA methylation is one of the key mechanisms underlying the epigenetic regulation of gene expression. During DNA replication, the methylation pattern of the parent strand is maintained on the replicated strand through the action of Dnmt1 (DNA Methyltransferase 1). In mammals, Dnmt1 is recruited to hemimethylated replication foci by Uhrf1 (Ubiquitin-like, Containing PHD and RING Finger Domains 1). Here we show that Uhrf1 is required for DNA methylation in vivo during zebrafish embryogenesis. Due in part to the early embryonic lethality of Dnmt1 and Uhrf1 knockout mice, roles for these proteins during lens development have yet to be reported. We show that zebrafish mutants in uhrf1 and dnmt1 have defects in lens development and maintenance. uhrf1 and dnmt1 are expressed in the lens epithelium, and in the absence of Uhrf1 or of catalytically active Dnmt1, lens epithelial cells have altered gene expression and reduced proliferation in both mutant backgrounds. This is correlated with a wave of apoptosis in the epithelial layer, which is followed by apoptosis and unraveling of secondary lens fibers. Despite these disruptions in the lens fiber region, lens fibers express appropriate differentiation markers. The results of lens transplant experiments demonstrate that Uhrf1 and Dnmt1 functions are required lens-autonomously, but perhaps not cell-autonomously, during lens development in zebrafish. These data provide the first evidence that Uhrf1 and Dnmt1 function is required for vertebrate lens development and maintenance.

Genes / Markers

Figures

Show all Figures

Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
WT	standard conditions	Day 5	ciliary marginal zone	ISH	Fig. S5
WT	standard conditions	Day 4	ciliary marginal zone	ISH	Fig. 5
WT	standard conditions	Day 5	lens epithelium	ISH	Fig. S5
WT	standard conditions	Day 4	lens epithelium	ISH	Fig. 5
dnmt1^s872/s872	standard conditions	Day 5	lens	IHC	Fig. 7
uhrf1^{hi3020Tg/hi3020Tg}	standard conditions	Day 5	lens	IHC	Fig. 7
WT	standard conditions	Day 5	lens	IHC	Fig. 7
dnmt1^s872/s872	standard conditions	Day 4	lens	ISH	Fig. 6
uhrf1^{hi3020Tg/hi3020Tg}	standard conditions	Day 4	lens	ISH	Fig. 6
WT	standard conditions	Day 4	lens	ISH	Fig. 6

1 - 10 of 16

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
dnmt1^s872/+; uhrf1^hi3020Tg/+	standard conditions	Day 5	eye morphology, normal	Fig. 4
dnmt1^s872/s872	standard conditions	Protruding-mouth	eye morphology, normal	Fig. S2
dnmt1^s872/s872	standard conditions	Day 5	DNA (cytosine-5-)-methyltransferase activity decreased occurrence, abnormal	Fig. 1
dnmt1^s872/s872	standard conditions	Day 5	DNA-methyltransferase activity decreased occurrence, abnormal	Fig. 1
dnmt1^s872/s872	standard conditions	Day 5	lens degenerate, abnormal	Fig. 3
dnmt1^s872/s872	standard conditions	Day 5	lens epithelium structure, abnormal	Fig. 3
dnmt1^s872/s872	standard conditions	Day 5	lens protruding, abnormal	Fig. 3
dnmt1^s872/s872	standard conditions	Day 5	lens structure, abnormal	Fig. 3
dnmt1^s872/s872	standard conditions	Day 5	retinal cone cell morphology, abnormal	Fig. S4
dnmt1^s872/s872	standard conditions	Day 5	retinal cone cell present, normal	Fig. S4

1 - 10 of 48

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hi3020Tg	Tg(nLacz-GTvirus)	Transgenic Insertion	uhrf1
s872		MNV	dnmt1
s904		Point Mutation	dnmt1

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
dnmt1^s872/s872
dnmt1^s872/s872; uhrf1^{hi3020Tg/hi3020Tg}
dnmt1^s872/+; uhrf1^hi3020Tg/+
dnmt1^s904/s904
uhrf1^{hi3020Tg/hi3020Tg}
WT

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Tittle et al., 2011 ZDB-PUB-101209-12 PMID:21126517

Uhrf1 and Dnmt1 are required for development and maintenance of the zebrafish lens

Tittle et al., 2011

ZDB-PUB-101209-12
PMID:21126517