PUBLICATION

Rdh10a Provides a Conserved Critical Step in the Synthesis of Retinoic Acid during Zebrafish Embryogenesis

Authors

D'Aniello, E., Ravisankar, P., Waxman, J.S.

ID

ZDB-PUB-150924-8

Date

2015

Source

PLoS One 10: e0138588 (Journal)

Registered Authors

Waxman, Joshua

Keywords

Embryos, Zebrafish, Eyes, Animal signaling and communication, Vitamin A, Xenopus, Phenotypes, Vertebrates

MeSH Terms

Alcohol Oxidoreductases/genetics
Alcohol Oxidoreductases/metabolism*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Zebrafish/embryology
Zebrafish/genetics
Zebrafish/metabolism*
In Situ Hybridization
PAX2 Transcription Factor/genetics
PAX2 Transcription Factor/metabolism
Gene Expression Regulation, Developmental
Body Patterning/drug effects
Body Patterning/genetics
Embryo, Nonmammalian/drug effects
Embryo, Nonmammalian/embryology
Embryo, Nonmammalian/metabolism*
Tretinoin/metabolism*
Tretinoin/pharmacology
Hot Temperature
Rhombencephalon/embryology
Rhombencephalon/metabolism
Vitamin A/pharmacology
Animals
Gene Knockdown Techniques
Retinaldehyde/pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Animals, Genetically Modified

(all 27)

PubMed

26394147 Full text @ PLoS One

Abstract

The first step in the conversion of vitamin A into retinoic acid (RA) in embryos requires retinol dehydrogenases (RDHs). Recent studies have demonstrated that RDH10 is a critical core component of the machinery that produces RA in mouse and Xenopus embryos. If the conservation of Rdh10 function in the production of RA extends to teleost embryos has not been investigated. Here, we report that zebrafish Rdh10a deficient embryos have defects consistent with loss of RA signaling, including anteriorization of the nervous system and enlarged hearts with increased cardiomyocyte number. While knockdown of Rdh10a alone produces relatively mild RA deficient phenotypes, Rdh10a can sensitize embryos to RA deficiency and enhance phenotypes observed when Aldh1a2 function is perturbed. Moreover, excess Rdh10a enhances embryonic sensitivity to retinol, which has relatively mild teratogenic effects compared to retinal and RA treatment. Performing Rdh10a regulatory expression analysis, we also demonstrate that a conserved teleost rdh10a enhancer requires Pax2 sites to drive expression in the eyes of transgenic embryos. Altogether, our results demonstrate that Rdh10a has a conserved requirement in the first step of RA production within vertebrate embryos.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cyp26a1	WT	standard conditions	14-19 somites	anatomical structure	ISH	Fig. 2
cyp26a1	WT + MO1-rdh10a + MO2-rdh10a + MO4-tp53	standard conditions	14-19 somites	anatomical structure	ISH	Fig. 2
cyp26a1	WT + MO1-rdh10a + MO2-rdh10a + MO4-tp53	standard conditions	14-19 somites	whole organism	RTPCR	Fig. 2
dhrs3a	WT	standard conditions	14-19 somites	anatomical structure	ISH	Fig. 2
dhrs3a	WT + MO1-rdh10a + MO2-rdh10a + MO4-tp53	standard conditions	14-19 somites	anatomical structure	ISH	Fig. 2
dhrs3a	WT + MO1-rdh10a + MO2-rdh10a + MO4-tp53	standard conditions	14-19 somites	whole organism	RTPCR	Fig. 2
DsRed2	f2Tg	chemical treatment: all-trans-retinal	Long-pec	cardiac muscle cell	IHC	Fig. 8
DsRed2	f2Tg	control	Long-pec	cardiac muscle cell	IHC	Fig. 8
DsRed2	f2Tg	chemical treatment: all-trans-retinol	Long-pec	cardiac muscle cell	IHC	Fig. 8
DsRed2	f2Tg	standard conditions	Long-pec	cardiac muscle cell	IHC	Fig. 3

1 - 10 of 36

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: all-trans-retinoic acid	Long-pec	caudal fin truncated, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinoic acid	Long-pec	caudal fin wholly posteriorized, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinoic acid	Long-pec	eye decreased size, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinoic acid	Long-pec	head decreased size, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinal	Long-pec	caudal fin truncated, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinal	Long-pec	caudal fin wholly posteriorized, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinal	Long-pec	eye decreased size, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinal	Long-pec	head decreased size, abnormal	Fig. 7
WT	chemical treatment: all-trans-retinol	Long-pec	caudal fin kinked, abnormal	Fig. 5
WT	chemical treatment: all-trans-retinol	Long-pec	caudal fin truncated, abnormal	Fig. 7

1 - 10 of 63

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
f2Tg	Tg(-5.1myl7:DsRed2-NLS)	Transgenic Insertion
i26		Point Mutation	aldh1a2
sk72Tg	Tg(12xRARE-eef1a1l1:EGFP)	Transgenic Insertion
x23Tg	Tg(hsp70l:pax2a)	Transgenic Insertion

1 - 4 of 4

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
pax2a	MO4-pax2a	MRPHLNO
pax2b	MO1-pax2b	MRPHLNO
rdh10a	MO1-rdh10a	MRPHLNO
rdh10a	MO2-rdh10a	MRPHLNO
tp53	MO4-tp53	MRPHLNO

Fish

Fish
aldh1a2^i26/i26
aldh1a2^i26/i26 + MO1-rdh10a + MO2-rdh10a + MO4-tp53
f2Tg
f2Tg + MO1-rdh10a + MO2-rdh10a + MO4-tp53
sk72Tg
sk72Tg + MO1-rdh10a + MO2-rdh10a + MO4-tp53
WT
WT + MO1-rdh10a + MO2-rdh10a + MO4-tp53

1 - 8 of 8

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed2	EFG	DsRed2
EGFP	EFG	EGFP

Mapping

D'Aniello et al., 2015 ZDB-PUB-150924-8 PMID:26394147

Rdh10a Provides a Conserved Critical Step in the Synthesis of Retinoic Acid during Zebrafish Embryogenesis

D'Aniello et al., 2015

ZDB-PUB-150924-8
PMID:26394147