PUBLICATION

Dual Roles of Fer Kinase Are Required for Proper Hematopoiesis and Vascular Endothelium Organization during Zebrafish Development

Authors: Dunn, E.M., Billquist, E.J., VanderStoep, A.L., Bax, P.G., Westrate, L.M., McLellan, L.K., Peterson, S.C., MacKeigan, J.P., Putzke, A.P.
ID: ZDB-PUB-171124-4
Date: 2017
Source: Biology 6(4): (Journal)
Registered Authors: Putzke, Aaron
Keywords: embryogenesis, erythrocyte, non-receptor tyrosine kinase, vasculature
MeSH Terms: none
PubMed: 29168762 Full text @ Biology (Basel)

Abstract

Fer kinase, a protein involved in the regulation of cell-cell adhesion and proliferation, has been shown to be required during invertebrate development and has been implicated in leukemia, gastric cancer, and liver cancer. However, in vivo roles for Fer during vertebrate development have remained elusive. In this study, we bridge the gap between the invertebrate and vertebrate realms by showing that Fer kinase is required during zebrafish embryogenesis for normal hematopoiesis and vascular organization with distinct kinase dependent and independent functions. In situ hybridization, quantitative PCR and fluorescence activated cell sorting (FACS) analyses revealed an increase in both erythrocyte numbers and gene expression patterns as well as a decrease in the organization of vasculature endothelial cells. Furthermore, rescue experiments have shown that the regulation of hematopoietic proliferation is dependent on Fer kinase activity, while vascular organizing events only require Fer in a kinase-independent manner. Our data suggest a model in which separate kinase dependent and independent functions of Fer act in conjunction with Notch activity in a divergent manner for hematopoietic determination and vascular tissue organization.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
DsRed	sd2Tg; y7Tg	standard conditions	Long-pec	hematopoietic cell	IFL	Fig. 4
DsRed	sd2Tg; y7Tg	standard conditions	Prim-5	hematopoietic cell	IFL	Fig. 4
DsRed	sd2Tg; y7Tg + MO3-fer	standard conditions	Prim-5	hematopoietic cell	IFL	Fig. 4
DsRed	sd2Tg; y7Tg + MO3-fer	standard conditions	Long-pec	hematopoietic cell	IFL	Fig. 4
EGFP	sd2Tg; y7Tg	standard conditions	Long-pec	vasculature	IFL	Fig. 4
EGFP	sd2Tg; y7Tg	standard conditions	Prim-5	vasculature	IFL	Fig. 4
EGFP	sd2Tg; y7Tg + MO3-fer	standard conditions	Prim-5	vasculature	IFL	Fig. 4
EGFP	sd2Tg; y7Tg + MO3-fer	standard conditions	Long-pec	vasculature	IFL	Fig. 4
fer	AB	standard conditions	Prim-5	brain anatomical region	ISH	Fig. 1
fer	AB	standard conditions	Prim-5	intermediate cell mass of mesoderm	ISH	Fig. 1

1 - 10 of 45

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO3-fer	standard conditions	5-9 somites	lateral plate mesoderm gata1a expression spatial pattern, abnormal	Fig. 6
AB + MO3-fer	standard conditions	5-9 somites	lateral plate mesoderm tal1 expression spatial pattern, abnormal	Fig. 6
AB + MO3-fer	standard conditions	5-9 somites	posterior lateral plate mesoderm runx1 expression decreased amount, abnormal	Fig. 6
AB + MO3-fer	standard conditions	5-9 somites	whole organism notch1a expression decreased amount, abnormal	Fig. 4
AB + MO3-fer	standard conditions	5-9 somites	whole organism notch1b expression decreased amount, abnormal	Fig. 4
AB + MO3-fer	standard conditions	5-9 somites	whole organism runx1 expression decreased amount, abnormal	Fig. 4
AB + MO3-fer	standard conditions	Prim-5	blood circulation decreased occurrence, abnormal	Fig. 3
AB + MO3-fer	standard conditions	Prim-5	blood island gata1a expression increased distribution, abnormal	Fig. 6
AB + MO3-fer	standard conditions	Prim-5	blood island hbbe2 expression increased distribution, abnormal	Fig. 6
AB + MO3-fer	standard conditions	Prim-5	blood island myb expression increased distribution, abnormal	Fig. 6

1 - 10 of 52

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
sd2Tg	Tg(gata1a:DsRed)	Transgenic Insertion
y7Tg	Tg(fli1:nEGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
fer	MO3-fer	MRPHLNO

Fish

Fish
AB
AB + MO3-fer
sd2Tg; y7Tg
sd2Tg; y7Tg + MO3-fer
y7Tg
y7Tg + MO3-fer

Antibodies

Orthology

Gene	Orthology
fer

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
EGFP	EFG	EGFP

Mapping

Dunn et al., 2017 ZDB-PUB-171124-4 PMID:29168762

Dual Roles of Fer Kinase Are Required for Proper Hematopoiesis and Vascular Endothelium Organization during Zebrafish Development

Dunn et al., 2017

ZDB-PUB-171124-4
PMID:29168762