PUBLICATION

Essential role of lysyl oxidases in notochord development

Authors

Gansner, J.M., Mendelsohn, B.A., Hultman, K.A., Johnson, S.L., and Gitlin, J.D.

ID

ZDB-PUB-070625-5

Date

2007

Source

Developmental Biology 307(2): 202-213 (Journal)

Registered Authors

Gitlin, Jonathan D., Hultman, Keith, Johnson, Stephen L.

Keywords

Zebrafish, Notochord, Lysyl oxidase, Copper, Nutrition, Disease model, col2a1

MeSH Terms

Notochord/abnormalities
Notochord/embryology*
Notochord/enzymology*
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/metabolism*
Gene Expression Regulation, Enzymologic
Protein-Lysine 6-Oxidase/antagonists & inhibitors
Protein-Lysine 6-Oxidase/genetics
Protein-Lysine 6-Oxidase/metabolism*
Gene Expression Regulation, Developmental
Animals
RNA, Antisense/genetics
DNA Primers/genetics
Zebrafish Proteins/antagonists & inhibitors
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Collagen Type II/genetics
Collagen Type II/metabolism
Models, Biological
Base Sequence
Phenotype

(all 22)

PubMed

17543297 Full text @ Dev. Biol.

Abstract

Recent studies reveal a critical role for copper in the development of the zebrafish notochord, suggesting that specific cuproenzymes are required for the structural integrity of the notochord sheath. We now demonstrate that beta-aminopropionitrile, a known inhibitor of the copper-dependent lysyl oxidases, causes notochord distortion in the zebrafish embryo identical to that seen in copper deficiency. Characterization of the zebrafish lysyl oxidase genes reveals eight unique sequences, several of which are expressed in the developing notochord. Specific gene knockdown demonstrates that loss of loxl1 results in notochord distortion, and that loxl1 and loxl5b have overlapping roles in notochord formation. Interestingly, while notochord abnormalities are not observed following partial knockdown of loxl1 or loxl5b alone, in each case this markedly sensitizes developing embryos to notochord distortion if copper availability is diminished. Likewise, partial knockdown of the lysyl oxidase substrate col2a1 results in notochord distortion when combined with reduced copper availability or partial knockdown of loxl1 or loxl5b. These data reveal a complex interplay of gene expression and nutrient availability critical to notochord development. They also provide insight into specific genetic and nutritional factors that may play a role in the pathogenesis of structural birth defects of the axial skeleton.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
col2a1a	WT	chemical treatment: neocuproine	Prim-5		floor plate	ISH	Fig. 7
col2a1a	WT	chemical treatment: beta-aminopropionitrile hemifumarate	Prim-5		floor plate	ISH	Fig. 7
col2a1a	WT	control	Prim-5		floor plate	ISH	Fig. 7
col2a1a	WT	chemical treatment: beta-aminopropionitrile hemifumarate	Prim-5		hypochord	ISH	Fig. 7
col2a1a	WT	chemical treatment: neocuproine	Prim-5		hypochord	ISH	Fig. 7
col2a1a	WT	control	Prim-5		hypochord	ISH	Fig. 7
col2a1a	WT	control	Prim-5	Not Detected	notochord	ISH	Fig. 7
col2a1a	WT	chemical treatment: neocuproine	Prim-5		notochord	ISH	Fig. 7
col2a1a	WT	chemical treatment: beta-aminopropionitrile hemifumarate	Prim-5		notochord	ISH	Fig. 7
col2a1a	WT	control	Prim-5	Not Detected	notochord	ISH	Fig. S4

1 - 10 of 58

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-col2a1a	standard conditions	Prim-5	notochord morphology, normal	Fig. 6
WT + MO1-col2a1a + MO1-loxl5b	standard conditions	Prim-5	notochord deformed, abnormal	Fig. 6
WT + MO1-loxl1	standard conditions	Prim-5	notochord deformed, abnormal	Fig. 5
WT + MO1-loxl1	standard conditions	Prim-5	somite morphology, abnormal	Fig. 5
WT + MO1-loxl1 + MO1-loxl5b	standard conditions	Prim-5	notochord deformed, abnormal	Fig. 7
WT + MO1-loxl1 + MO1-loxl5b	standard conditions	Prim-5	notochord deformed, abnormal	Fig. 5
WT + MO1-loxl1 + MO1-loxl5b	standard conditions	Prim-5	somite morphology, abnormal	Fig. 5
WT + MO1-loxl2b	standard conditions	Prim-5	notochord kinked, abnormal	Fig. 5
WT + MO1-loxl3b	standard conditions	Prim-5	notochord kinked, abnormal	Fig. 5
WT + MO1-loxl5b	standard conditions	Prim-15	notochord morphology, normal	Fig. 6

1 - 10 of 18

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
col2a1a	MO1-col2a1a	MRPHLNO
loxl1	MO1-loxl1	MRPHLNO
loxl1	MO2-loxl1	MRPHLNO
loxl1	MO3-loxl1	MRPHLNO
loxl2b	MO1-loxl2b	MRPHLNO
loxl3b	MO1-loxl3b	MRPHLNO
loxl5b	MO1-loxl5b	MRPHLNO
loxl5b	MO2-loxl5b	MRPHLNO

1 - 8 of 8

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Fish

Fish
WT
WT + MO1-col2a1a
WT + MO1-col2a1a + MO1-loxl5b
WT + MO1-loxl1
WT + MO1-loxl1 + MO1-loxl5b
WT + MO1-loxl2b
WT + MO1-loxl3b
WT + MO1-loxl5b
WT + MO1-loxl5b + MO2-loxl1
WT + MO2-loxl1

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Antibodies

Orthology

Gene	Orthology
loxa
loxl1
loxl2a
loxl2b
loxl3a
loxl3b

Engineered Foreign Genes

Mapping

Gansner et al., 2007 ZDB-PUB-070625-5 PMID:17543297

Essential role of lysyl oxidases in notochord development

Gansner et al., 2007

ZDB-PUB-070625-5
PMID:17543297