PUBLICATION

Phosphoribosyl pyrophosphate synthetase polymerization influences lens fiber organization in zebrafish

Authors

Begovich, K., Yelon, D., Wilhelm, J.E.

ID

ZDB-PUB-200422-10

Date

2020

Source

Developmental Dynamics : an official publication of the American Association of Anatomists 249(8): 1018-1031 (Journal)

Registered Authors

Yelon, Deborah

Keywords

PRPS, actin, lens fiber, metabolic enzyme filaments, retina

MeSH Terms

Mutation
Retina/embryology
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism*
Eye/embryology
Eye/growth & development
Ribose-Phosphate Pyrophosphokinase/genetics*
Ribose-Phosphate Pyrophosphokinase/metabolism*
Gene Expression Regulation, Developmental
Pigmentation
Genotype
Retinal Pigment Epithelium/embryology
Air Sacs/embryology
Zebrafish/embryology*
Zebrafish/genetics
Microscopy, Fluorescence
Alleles
Polymerization
Animals
Actins/metabolism
Lens, Crystalline/embryology*
Lens, Crystalline/growth & development*

(all 22)

PubMed

32243675 Full text @ Dev. Dyn.

Abstract

Background The self-assembly of metabolic enzymes into filaments or foci highlights an intriguing mechanism for the regulation of metabolic activity. Recently, we identified the conserved polymerization of phosphoribosyl pyrophosphate synthetase (PRPS), which catalyzes the first step in purine nucleotide synthesis, in yeast and cultured mammalian cells. While previous work has revealed that loss of PRPS activity regulates retinal development in zebrafish, the extent to which PRPS filament formation affects tissue development remains unknown.

Results By generating novel alleles in the zebrafish PRPS paralogs, prps1a and prps1b, we gained new insight into the role of PRPS filaments during eye development. We found that mutations in prps1a alone are sufficient to generate abnormally small eyes along with defects in head size, pigmentation, and swim bladder inflation. Furthermore, a loss-of-function mutation that truncates the Prps1a protein resulted in the failure of PRPS filament assembly. Lastly, in mutants that fail to assemble PRPS filaments, we observed disorganization of the actin network in the lens fibers.

Conclusions The truncation of Prps1a blocked PRPS filament formation and resulted in a disorganized lens fiber actin network. Altogether, these findings highlight a potential role for PRPS filaments during lens fiber organization in zebrafish.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
prps1a	prps1a^sd59/sd59	standard conditions	Day 5	eye	IHC	Fig. 5
prps1a	prps1a^sd59/sd59	standard conditions	Day 5	eye	IHC	Fig. 6
prps1a	prps1a^sd60/sd60	standard conditions	Day 5	eye	IHC	Fig. 5
prps1a	prps1a^sd60/sd60	standard conditions	Day 5	eye	IHC	Fig. 6
prps1a	prps1b^sd61/sd61	standard conditions	Day 5	eye	IHC	Fig. 6
prps1a	prps1b^sd61/sd61	standard conditions	Day 5	eye	IHC	Fig. 5
prps1a	WT	standard conditions	Day 5	eye	IHC	Fig. 6
prps1a	WT	standard conditions	Day 5	eye	IHC	Fig. 1
prps1a	WT	standard conditions	Day 5	eye	IHC	Fig. 5
prps1b	prps1a^sd59/sd59	standard conditions	Day 5	eye	IHC	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
prps1a^sd59/sd59	standard conditions	Long-pec	eye actin filament organized, normal	Fig. 6
prps1a^sd59/sd59	standard conditions	Long-pec	eye decreased size, abnormal	Fig. 4
prps1a^sd59/sd59	standard conditions	Long-pec	retina decreased size, abnormal	Fig. 4
prps1a^sd59/sd59	standard conditions	Day 5	establishment of cell polarity process quality, normal	Fig. 7
prps1a^sd59/sd59	standard conditions	Day 5	eye prps1a expression spatial pattern, abnormal	Fig. 6
prps1a^sd59/sd59	standard conditions	Day 5	eye prps1a expression spatial pattern, abnormal	Fig. 5
prps1a^sd59/sd59	standard conditions	Day 5	eye prps1b expression spatial pattern, abnormal	Fig. 6
prps1a^sd59/sd59	standard conditions	Day 5	eye prps1b expression spatial pattern, abnormal	Fig. 5
prps1a^sd59/sd59	standard conditions	Day 5	eye actin filament disorganized, abnormal	Fig. 6
prps1a^sd59/sd59	standard conditions	Day 5	head decreased size, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
sd59	Small Deletion	prps1a
sd60	Small Deletion	prps1a
sd61	Indel	prps1b

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
prps1a	CRISPR5-prps1a	CRISPR
prps1a	CRISPR6-prps1a	CRISPR
prps1b	CRISPR1-prps1b	CRISPR

Fish

Fish
prps1a^sd59/sd59
prps1a^sd60/sd60
prps1b^sd61/sd61
WT

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Begovich et al., 2020 ZDB-PUB-200422-10 PMID:32243675

Phosphoribosyl pyrophosphate synthetase polymerization influences lens fiber organization in zebrafish

Begovich et al., 2020

ZDB-PUB-200422-10
PMID:32243675