PUBLICATION

Chordacentrum mineralization is delayed in zebrafish betaglycan-null mutants

Authors

Molina-Villa, T., Ramírez-Vidal, L., Mendoza, V., Escalante-Alcalde, D., López-Casillas, F.

ID

ZDB-PUB-210707-9

Date

2021

Source

Developmental Dynamics : an official publication of the American Association of Anatomists 251(1): 213-225 (Journal)

Registered Authors

Lopez-Casillas, Fernando, Mendoza, Valentin, Ramirez-Vidal, Lizbeth

Keywords

none

MeSH Terms

Proteoglycans/genetics
Mice
Zebrafish*/genetics
Zebrafish*/metabolism
Animals
Receptors, Transforming Growth Factor beta*/genetics
Receptors, Transforming Growth Factor beta*/metabolism
Signal Transduction/genetics
Transforming Growth Factor beta/genetics
Transforming Growth Factor beta/metabolism

(all 10)

PubMed

34228380 Full text @ Dev. Dyn.

Abstract

Background The Transforming Growth Factor β (TGFβ) family is a group of related proteins that signal through a type I and type II receptors. Betaglycan, also known as the type III receptor (Tgfbr3), is a co-receptor for various ligands of the TGFβ family that participates in heart, liver and kidney development as revealed by the tgfbr3-null mouse, as well as in angiogenesis as revealed by Tgfbr3 downregulation in morphant zebrafish.

Results Here we present CRISPR/Cas9-derived zebrafish Tgfbr3-null mutants, which exhibited unaltered embryonic angiogenesis and developed into fertile adults. One reproducible phenotype displayed by these Tgfbr3-null mutants is delayed chordacentra mineralization, which nonetheless does not result in vertebral abnormalities in the adult fishes. We also report that the canonical TGFβ signaling pathway is needed for proper chordacentra mineralization and that Tgfbr3 absence decreases this signal in the notochordal cells responsible for this process.

Conclusion Betaglycan's "ligand presentation" function contributes to the optimal TGFβ signaling required for zebrafish chordacentra mineralization. This article is protected by copyright. All rights reserved.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bmp2b	tgfbr3^{una202/una202}; y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
bmp2b	y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
eng	tgfbr3^{una202/una202}; y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
eng	y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
tgfb1a	tgfbr3^{una202/una202}; y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
tgfb1a	y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
tgfb2	tgfbr3^{una202/una202}; y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
tgfb2	y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
tgfb3	tgfbr3^{una202/una202}; y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4
tgfb3	y1Tg	standard conditions	Day 6	whole organism	RTPCR	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
tgfbr3^una201/+; tgfbr3^una202/+; y1Tg	standard conditions	Protruding-mouth	whole organism morphology, normal	Fig. 1
tgfbr3^una201/+; tgfbr3^una202/+; y1Tg	standard conditions	Protruding-mouth	whole organism viable, normal	Fig. 1
tgfbr3^{una201/una201}; y1Tg	standard conditions	Protruding-mouth	whole organism morphology, normal	Fig. 1
tgfbr3^{una201/una201}; y1Tg	standard conditions	Protruding-mouth	whole organism viable, normal	Fig. 1
tgfbr3^una202/+; tgfbr3^una203/+; y1Tg	standard conditions	Protruding-mouth	whole organism morphology, normal	Fig. 1
tgfbr3^una202/+; tgfbr3^una203/+; y1Tg	standard conditions	Protruding-mouth	whole organism viable, normal	Fig. 1
tgfbr3^{una202/una202}; y1Tg	standard conditions	Long-pec	dorsal aorta normal diameter, normal	Fig. 2
tgfbr3^{una202/una202}; y1Tg	standard conditions	Long-pec	intersegmental vessel normal diameter, normal	Fig. 2
tgfbr3^{una202/una202}; y1Tg	standard conditions	Long-pec	intersegmental vessel spatial pattern, normal	Fig. 2
tgfbr3^{una202/una202}; y1Tg	standard conditions	Long-pec	whole organism tgfbr3 expression absent, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
una201		Small Deletion	tgfbr3
una202		Small Deletion	tgfbr3
una203		Indel	tgfbr3
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
tgfbr3	CRISPR3-tgfbr3	CRISPR
tgfbr3	MO2-tgfbr3	MRPHLNO

Fish

Fish
tgfbr3^una201/+; tgfbr3^una202/+; y1Tg
tgfbr3^{una201/una201}; y1Tg
tgfbr3^una202/+; tgfbr3^una203/+; y1Tg
tgfbr3^{una202/una202}; y1Tg
tgfbr3^{una202/una202}; y1Tg
tgfbr3^{una202/una202}; y1Tg + MO2-tgfbr3
tgfbr3^{una203/una203}; y1Tg
WT
y1Tg
y1Tg + MO2-tgfbr3

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Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-tgfbr3		tgfbr3		Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Molina-Villa et al., 2021 ZDB-PUB-210707-9 PMID:34228380

Chordacentrum mineralization is delayed in zebrafish betaglycan-null mutants

Molina-Villa et al., 2021

ZDB-PUB-210707-9
PMID:34228380