PUBLICATION

Genome-wide Analysis of the Zebrafish Klf Family Identifies Two Genes important for Erythroid Maturation

Authors

Xue, Y., Gao, S., Liu, F.

ID

ZDB-PUB-150528-4

Date

2015

Source

Developmental Biology 403(2): 115-27 (Journal)

Registered Authors

Gao, Shuai, Liu, Feng

Keywords

Klf family, Klf3, Klf6a, erythropoiesis, zebrafish

MeSH Terms

Phylogeny
Kruppel-Like Transcription Factors/genetics*
Kruppel-Like Transcription Factors/metabolism*
Erythroid Cells/cytology
Erythroid Cells/metabolism*
Cyclin-Dependent Kinase Inhibitor p21/metabolism
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism*
Gene Expression
Embryo, Nonmammalian/metabolism
Animals
Zebrafish

(all 12)

PubMed

26015096 Full text @ Dev. Biol.

Abstract

Krüppel-like transcription factors (Klfs), each of which contains a CACCC-box binding domain, have been investigated in a variety of developmental processes, such as angiogenesis, neurogenesis and somatic-cell reprogramming. However, the function and molecular mechanism by which the Klf family acts during developmental hematopoiesis remain elusive. Here, we report identification of 24 Klf family genes in zebrafish using bioinformatics. Gene expression profiling shows that 6 of these genes are expressed in blood and/or vascular endothelial cells during embryogenesis. Loss of function of 2 factors (klf3 or klf6a) leads to a decreased number of mature erythrocytes. Molecular studies indicate that both Klf3 and Klf6a are essential for erythroid cell differentiation and maturation but that these two proteins function in distinct manners. We find that Klf3 inhibits the expression of ferric-chelate reductase 1b (frrs1b), thereby promoting the maturation of erythroid cells, whereas Klf6a controls the erythroid cell cycle by negatively regulating cdkn1a expression to determine the rate of red blood cell proliferation. Taken together, our study provides a global view of the Klf family members that contribute to hematopoiesis in zebrafish and sheds new light on the function and molecular mechanism by which Klf3 and Klf6a act during erythropoiesis in vertebrates.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
DsRed	sd2Tg	standard conditions	Long-pec	intermediate cell mass of mesoderm	IHC	Fig. 6
DsRed	sd2Tg + MO1-klf6a	standard conditions	Long-pec	intermediate cell mass of mesoderm	IHC	Fig. 6
frrs1b	WT	standard conditions	Prim-5	intermediate cell mass of mesoderm	ISH	Fig. 4
frrs1b	WT + MO1-klf3	standard conditions	Prim-5	intermediate cell mass of mesoderm	ISH	Fig. 4
gata1a	WT	standard conditions	Prim-5	erythroid lineage cell	ISH	Fig. 3
gata1a	WT	standard conditions	Prim-5	erythroid lineage cell	ISH	Fig. 5
gata1a	WT + MO1-klf3	standard conditions	Prim-5	erythroid lineage cell	ISH	Fig. 3
gata1a	WT + MO1-klf6a	standard conditions	Prim-5	erythroid lineage cell	ISH	Fig. 5
hbbe1.1	WT	standard conditions	Prim-25	erythroid lineage cell	ISH	Fig. 3
hbbe1.1	WT	standard conditions	Long-pec	erythroid lineage cell	ISH	Fig. 5

1 - 10 of 108

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-klf3	standard conditions	Prim-25	nucleate erythrocyte decreased amount, abnormal	Fig. 3
WT + MO1-klf3	standard conditions	Prim-25	primitive erythrocyte differentiation decreased process quality, abnormal	Fig. 3
WT + MO1-klf3	standard conditions	Long-pec	nucleate erythrocyte decreased amount, abnormal	Fig. 4
WT + MO1-klf3	standard conditions	Long-pec	nucleate erythrocyte decreased amount, abnormal	Fig. 3
WT + MO1-klf3	standard conditions	Pec-fin	erythrocyte maturation arrested, abnormal	Fig. 3
WT + MO1-klf3	standard conditions	Pec-fin	erythrocyte maturation decreased process quality, abnormal	Fig. 3
WT + MO1-klf3	standard conditions	Pec-fin	primitive erythrocyte differentiation decreased process quality, abnormal	Fig. 3
WT + MO1-klf6a	standard conditions	Prim-25	nucleate erythrocyte decreased amount, abnormal	Fig. 5
WT + MO1-klf6a	standard conditions	Long-pec	nucleate erythrocyte decreased amount, abnormal	Fig. 5
WT + MO1-klf6a	standard conditions	Long-pec	nucleate erythrocyte decreased amount, abnormal	Fig. 6

1 - 10 of 14

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
m378		Unknown	npas4l
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion
sd2Tg	Tg(gata1a:DsRed)	Transgenic Insertion
tg234		Point Mutation	trim33
y11		Insertion	etsrp
zdf1		Point Mutation	tp53

1 - 6 of 6

Show

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cdkn1a	MO1-cdkn1a	MRPHLNO
frrs1b	MO1-frrs1b	MRPHLNO
klf3	MO1-klf3	MRPHLNO
klf6a	MO1-klf6a	MRPHLNO
tp53	MO4-tp53	MRPHLNO

Fish

Fish
etsrp^y11/y11
npas4l^m378/m378
sd2Tg
sd2Tg + MO1-klf6a
tp53^zdf1/zdf1
tp53^zdf1/zdf1 + MO1-klf6a
trim33^tg234/tg234
WT
WT + MO1-cdkn1a + MO1-klf6a
WT + MO1-frrs1b + MO1-klf3

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
EGFP	EFG	EGFP

Mapping

Xue et al., 2015 ZDB-PUB-150528-4 PMID:26015096

Genome-wide Analysis of the Zebrafish Klf Family Identifies Two Genes important for Erythroid Maturation

Xue et al., 2015

ZDB-PUB-150528-4
PMID:26015096