PUBLICATION

Restriction of retinoic acid activity by Cyp26b1 is required for proper timing and patterning of osteogenesis during zebrafish development

Authors

Laue, K., Jänicke, M., Plaster, N., Sonntag, C., and Hammerschmidt, M.

ID

ZDB-PUB-081022-35

Date

2008

Source

Development (Cambridge, England) 135(22): 3775-3787 (Journal)

Registered Authors

Hammerschmidt, Matthias, Laue, Kathrin, Plaster, Nikki, Sonntag, Carmen

Keywords

Cyp26b1, Retinoic acid, Bmp2, Cartilage, Bone, Chondrocyte, Osteoblast, Osteopontin, Osterix, Craniofacial development, Vertebra, Zebrafish

MeSH Terms

Branchial Region/embryology
Branchial Region/enzymology
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Osteoblasts/enzymology
Mice
Osteopontin/metabolism
Gene Expression Regulation, Enzymologic
Cytochrome P-450 Enzyme System/genetics
Cytochrome P-450 Enzyme System/metabolism*
Body Patterning*
Tretinoin/metabolism*
Gene Expression Regulation, Developmental*
Mutation/genetics
Bone Morphogenetic Protein 2/genetics
Bone Morphogenetic Protein 2/metabolism
Base Sequence
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/metabolism*
Animals
Phenotype
Osteogenesis*
Animals, Genetically Modified

(all 24)

PubMed

18927157 Full text @ Development

Abstract

Skeletal syndromes are among the most common birth defects. Vertebrate skeletogenesis involves two major cell types: cartilage-forming chondrocytes and bone-forming osteoblasts. In vitro, both are under the control of retinoic acid (RA), but its exact in vivo effects remained elusive. Here, based on the positional cloning of the dolphin mutation, we have studied the role of the RA-oxidizing enzyme Cyp26b1 during cartilage and bone development in zebrafish. cyp26b1 is expressed in condensing chondrocytes as well as in osteoblasts and their precursors. cyp26b1 mutants and RA-treated wild-type fish display a reduction in midline cartilage and the hyperossification of facial and axial bones, leading to fusions of vertebral primordia, a defect not previously described in the context of RA signaling. Fusions of cervical vertebrae were also obtained by treating mouse fetuses with the specific Cyp26 inhibitor R115866. Together with data on the expression of osteoblast markers, our results indicate that temporal and spatial restriction of RA signaling by Cyp26 enzymes is required to attenuate osteoblast maturation and/or activity in vivo. cyp26b1 mutants may serve as a model to study the etiology of human vertebral disorders such as Klippel-Feil anomaly.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
col10a1a	cyp26b1^{ti230g/ti230g}	standard conditions	Day 5	opercle osteoblast	ISH	Fig. 8
col10a1a	cyp26b1^{ti230g/ti230g}	standard conditions	Day 6	vertebra osteoblast	ISH	Fig. 8
col10a1a	fr13Tg	heat shock	Day 6	vertebra osteoblast	ISH	Fig. 8
col10a1a	WT	standard conditions	Day 5	ceratohyal cartilage perichondrium	ISH	Fig. 2
col10a1a	WT	standard conditions	Day 5	opercle osteoblast	ISH	Fig. 8
col10a1a	WT	standard conditions	Day 6	vertebra osteoblast	ISH	Fig. 3
col10a1a	WT	standard conditions	Day 6	vertebra osteoblast	ISH	Fig. 8
col10a1a	WT	standard conditions	Day 5	vertebra osteoblast	ISH	Fig. 3
col10a1a	WT	standard conditions	Protruding-mouth	vertebra osteoblast	ISH	Fig. 3
col2a1a	cyp26b1^{ti230g/ti230g}	standard conditions	Long-pec	neurocranium chondrocyte	ISH	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO5-cyp26b1	standard conditions	Day 5	basibranchial malformed, abnormal	Fig. 4
WT + MO5-cyp26b1	standard conditions	Day 5	ethmoid cartilage decreased size, abnormal	Fig. 4
WT + MO5-cyp26b1	standard conditions	Day 5	ethmoid cartilage malformed, abnormal	Fig. 4
WT + MO5-cyp26b1	standard conditions	Day 5	parachordal cartilage malformed, abnormal	Fig. 4
WT + MO5-cyp26b1	standard conditions	Days 7-13	centrum ossified, abnormal	Fig. 6
WT + MO5-cyp26b1	standard conditions	Days 7-13	hyosymplectic cartilage composition, abnormal	Fig. 5
WT + MO5-cyp26b1	standard conditions	Days 7-13	opercle increased size, abnormal	Fig. 5
WT + MO5-cyp26b1	standard conditions	Days 7-13	regulation of ossification disrupted, abnormal	Fig. 5
WT + MO5-cyp26b1	standard conditions	Days 7-13	regulation of ossification disrupted, abnormal	Fig. 6
cyp26b1^ti230g/+	standard conditions	Days 7-13	centrum ossified, abnormal	Fig. 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fr13Tg	Tg(hsp70l:bmp2b)	Transgenic Insertion
sa2		Point Mutation	cyp26b1
ti230g		Unknown	cyp26b1
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
aldh1a2	MO1-aldh1a2	MRPHLNO
aldh1a2	MO2-aldh1a2	MRPHLNO
cyp26b1	MO5-cyp26b1	MRPHLNO

Fish

Fish
cyp26b1^ti230g/+
cyp26b1^{ti230g/ti230g}
cyp26b1^{ti230g/ti230g} + MO1-aldh1a2 + MO2-aldh1a2
fr13Tg
WT
WT + MO5-cyp26b1
y1Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Entity Type	Entity Symbol	Location
Feature	ti230g	Chr: 7 Details
GENE	cyp26b1	Chr: 7 Details

Laue et al., 2008 ZDB-PUB-081022-35 PMID:18927157

Restriction of retinoic acid activity by Cyp26b1 is required for proper timing and patterning of osteogenesis during zebrafish development

Laue et al., 2008

ZDB-PUB-081022-35
PMID:18927157