PUBLICATION

Nodal Signaling Range Is Regulated by Proprotein Convertase-Mediated Maturation

Authors

Tessadori, F., Noël, E.S., Rens, E.G., Magliozzi, R., Evers-van Gogh, I.J., Guardavaccaro, D., Merks, R.M., Bakkers, J.

ID

ZDB-PUB-150217-3

Date

2015

Source

Developmental Cell 32(5): 631-9 (Journal)

Registered Authors

Bakkers, Jeroen, Noël, Emily

Keywords

none

MeSH Terms

Molecular Sequence Data
Zebrafish/growth & development*
Zebrafish/metabolism*
Left-Right Determination Factors/metabolism*
Amino Acid Sequence
Mesoderm/cytology
Mesoderm/metabolism
In Situ Hybridization
Zebrafish Proteins/metabolism*
Body Patterning/physiology
Nodal Protein/metabolism*
Animals
Fluorescent Antibody Technique
Blotting, Western
Signal Transduction*
Sequence Homology, Amino Acid
Proprotein Convertases/metabolism*
RNA, Messenger/genetics

(all 18)

PubMed

25684355 Full text @ Dev. Cell

Abstract

Tissue patterning is established by extracellular growth factors or morphogens. Although different theoretical models explaining specific patterns have been proposed, our understanding of tissue pattern establishment in vivo remains limited. In many animal species, left-right patterning is governed by a reaction-diffusion system relying on the different diffusivity of an activator, Nodal, and an inhibitor, Lefty. In a genetic screen, we identified a zebrafish loss-of-function mutant for the proprotein convertase FurinA. Embryological and biochemical experiments demonstrate that cleavage of the Nodal-related Spaw proprotein into a mature form by FurinA is required for Spaw gradient formation and activation of Nodal signaling. We demonstrate that FurinA is required cell-autonomously for the long-range signaling activity of Spaw and no other Nodal-related factors. Combined in silico and in vivo approaches support a model in which FurinA controls the signaling range of Spaw by cleaving its proprotein into a mature, extracellular form, consequently regulating left-right patterning.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
foxa3	furina^hu119/hu119	standard conditions	Long-pec	gut	ISH	Fig. 1
foxa3	furina^hu119/hu119	standard conditions	Long-pec	gut	ISH	Fig. 1
foxa3	furina^hu119/hu119	standard conditions	Long-pec	liver	ISH	Fig. 1
foxa3	furina^hu119/hu119	standard conditions	Long-pec	liver	ISH	Fig. 1
foxa3	furina^hu119/hu119	standard conditions	Long-pec	pancreas	ISH	Fig. 1
foxa3	furina^hu119/hu119	standard conditions	Long-pec	pancreas	ISH	Fig. 1
foxa3	WT	standard conditions	Long-pec	gut	ISH	Fig. 1
foxa3	WT	standard conditions	Long-pec	liver	ISH	Fig. 1
foxa3	WT	standard conditions	Long-pec	pancreas	ISH	Fig. 1
furina	spaw^{t30973/t30973}	standard conditions	20-25 somites	whole organism	ISH	Fig. S1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
furina^hu119/+; furina^td204e/+	standard conditions	Long-pec	heart jogging process quality, abnormal	Fig. S1
furina^hu119/hu119	standard conditions	20-25 somites	determination of heart left/right asymmetry process quality, abnormal	Fig. S1
furina^hu119/hu119	standard conditions	20-25 somites	determination of heart left/right asymmetry process quality, abnormal	Fig. S1
furina^hu119/hu119	standard conditions	20-25 somites	determination of left/right asymmetry in lateral mesoderm process quality, abnormal	Fig. S1
furina^hu119/hu119	standard conditions	20-25 somites	determination of left/right asymmetry in lateral mesoderm process quality, abnormal	Fig. S1
furina^hu119/hu119	standard conditions	Prim-5	caudal fin morphology, abnormal	Fig. 1
furina^hu119/hu119	standard conditions	Prim-5	determination of heart left/right asymmetry process quality, abnormal	Fig. 1
furina^hu119/hu119	standard conditions	Prim-5	heart position, abnormal	Fig. 1
furina^hu119/hu119	standard conditions	Prim-15	determination of heart left/right asymmetry process quality, abnormal	Fig. 1
furina^hu119/hu119	standard conditions	Prim-15	heart position, abnormal	Fig. 1

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hu119		Point Mutation	furina
kca4Tg	Tg(-1.5hsp70l:GAL4)	Transgenic Insertion
t30973		Point Mutation	spaw
td204e		Point Mutation	furina

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
furina^hu119/hu119
furina^hu119/hu119
furina^hu119/+; furina^td204e/+
furina^{td204e/td204e}
kca4Tg
spaw^{t30973/t30973}
WT

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-actb	monoclonal		IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GAL4	EFG	GAL4

Mapping

Tessadori et al., 2015 ZDB-PUB-150217-3 PMID:25684355

Nodal Signaling Range Is Regulated by Proprotein Convertase-Mediated Maturation

Tessadori et al., 2015

ZDB-PUB-150217-3
PMID:25684355