PUBLICATION

CFTR is required for the migration of Primordial Germ Cells during zebrafish early embryogenesis

Authors

Liao, H., Chen, Y., Yulong, L., Xue, S., Liu, M., Lin, Z., Liu, Y., Chan, H.C., Zhang, X., Sun, H.

ID

ZDB-PUB-180624-4

Date

2018

Source

Reproduction (Cambridge, England) 156(3): 261-268 (Journal)

Registered Authors

Chan, Hsiao Chang, Sun, Huaqin

Keywords

none

MeSH Terms

Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors
Cystic Fibrosis Transmembrane Conductance Regulator/genetics
Cystic Fibrosis Transmembrane Conductance Regulator/physiology*
Cell Movement/physiology*
Frameshift Mutation
Embryo, Nonmammalian/physiology*
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/physiology
Base Sequence
Germ Cells/physiology*
Embryonic Development
Animals

(all 13)

PubMed

29930176 Full text @ Reproduction

Abstract

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene affect fertility in both sexes. However, the involvement of CFTR in regulating germ cell development remains largely unknown. Here, we used zebrafish model to investigate the role of CFTR in primordial germ cells (PGCs) development. We generated a cftr frameshift mutant zebrafish line using CRISPR/Cas9 technique and investigated the migration of PGCs during early embryo development. Our results showed that loss of Cftr impairs the migration of PGCs from dome stages onward. The migration of PGCs was also perturbed by treatment of CFTRinh-172, a gating-speciﬁc CFTR channel inhibitor. Moreover, defected PGCs migration in cftr mutant embryos can be partially rescued by injection of WT but not other channel-defective mutant cftr mRNAs. Finally, we observed the elevation of cxcr4b, cxcl12a, rgs14a and ca15b, key factors involved in zebrafish PGCs migration, in cftr-mutant zebrafish embryos. Taken together, the present study revealed an important role of CFTR acting as an ion channel in regulating PGCs migration during early embryogenesis. Defect of which may impair germ cell development through elevation of key factors involved in cell motility and response to chemotactic gradient in PGCs.

Genes / Markers

Figures

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Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
ca15b		AB	standard conditions	50%-epiboly	primordial germ cell	ISH	Fig. 5
ca15b		AB	standard conditions	50%-epiboly	whole organism	RTPCR	Fig. 5
ca15b		cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	primordial germ cell	ISH	Fig. 5
ca15b		cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	whole organism	RTPCR	Fig. 5
cftr	Ab2-cftr	AB	standard conditions	Prim-5	whole organism	WB	Fig. 1
cftr	Ab2-cftr	cftr^{scu101/scu101} (AB)	standard conditions	Prim-5	whole organism	WB	Fig. 1
cxcl12a		AB	standard conditions	50%-epiboly	whole organism	RTPCR	Fig. 5
cxcl12a		cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	whole organism	RTPCR	Fig. 5
cxcr4b		AB	standard conditions	50%-epiboly	whole organism	RTPCR	Fig. 5
cxcr4b		cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	whole organism	RTPCR	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	chemical treatment by environment: CFTRinh-172	50%-epiboly	germ cell migration decreased occurrence, abnormal	Fig. 3
AB	chemical treatment by environment: CFTRinh-172	50%-epiboly	primordial germ cell mislocalised, abnormal	Fig. 3
cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	germ cell migration decreased occurrence, abnormal	Fig. 5
cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	germ cell migration decreased occurrence, abnormal	Fig. 4
cftr^{scu101/scu101} (AB)	standard conditions	Dome	germ cell migration decreased occurrence, abnormal	Fig. 2
cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	germ cell migration decreased occurrence, abnormal	Fig. 2
cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	primordial germ cell mislocalised, abnormal	Fig. 5
cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	primordial germ cell mislocalised, abnormal	Fig. 4
cftr^{scu101/scu101} (AB)	standard conditions	Dome	primordial germ cell mislocalised, abnormal	Fig. 2
cftr^{scu101/scu101} (AB)	standard conditions	50%-epiboly	primordial germ cell mislocalised, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
scu101		Small Deletion	cftr

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cftr	CRISPR1-cftr	CRISPR

Fish

Fish
AB
cftr^{scu101/scu101} (AB)

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab2-cftr	monoclonal	cftr	IgM	Mouse

Orthology

Engineered Foreign Genes

Mapping

Liao et al., 2018 ZDB-PUB-180624-4 PMID:29930176

CFTR is required for the migration of Primordial Germ Cells during zebrafish early embryogenesis

Liao et al., 2018

ZDB-PUB-180624-4
PMID:29930176