PUBLICATION

Neph3 associates with regulation of glomerular and neural development in zebrafish

Authors

Wang, H., Lehtonen, S., Chen, Y.C., Heikkilä, E., Panula, P., and Holthöfer, H.

ID

ZDB-PUB-111122-36

Date

2012

Source

Differentiation; research in biological diversity 83(1): 38-46 (Journal)

Registered Authors

Panula, Pertti

Keywords

kidney development, glomerulus, podocyte, Neph3, kirrel2, zebrafish

MeSH Terms

Animals
Brain/anatomy & histology
Brain/embryology
Gene Expression Regulation, Developmental
Intracellular Signaling Peptides and Proteins/genetics
Intracellular Signaling Peptides and Proteins/metabolism
Kidney Glomerulus/anatomy & histology
Kidney Glomerulus/embryology*
Kidney Glomerulus/metabolism
Membrane Proteins/genetics*
Membrane Proteins/metabolism
Nephrons/embryology*
Nephrons/growth & development
Neurogenesis/genetics
Oligodeoxyribonucleotides, Antisense/genetics
Podocytes/metabolism
Pronephros/embryology
Pronephros/growth & development
RNA, Messenger/genetics
Zebrafish/embryology*
Zebrafish/genetics*
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism

(all 23)

PubMed

22099175 Full text @ Differentiation

Abstract

Neph3 (filtrin) is a membrane protein expressed in the glomerular epithelial cells (podocytes), but its role in the glomerulus is still largely unknown. To characterize the function of Neph3 in the glomerulus, we employed the zebrafish as a model system. Here we show that the expression of neph3 in pronephros starts before the onset of nephrin and podocin expression, peaks when the nephron primordium differentiates into glomerulus and tubulus, and is then downregulated upon glomerular maturation. By histology, we found that neph3 is specifically expressed in pronephric podocytes at 36 hpf. Furthermore, disruption of neph3 expression by antisense morpholino oligonucleotides results in distorted body curvature and transient pericardial edema, the latter likely reflecting perturbation of glomerular osmoregulatory function. Histological analysis of neph3 morphants reveals altered glomerular morphology and dilated pronephric tubules. The phenotype of neph3 morphants, curved body and pericardial edema, is rescued by wild-type zebrafish neph3 mRNA. In addition to glomerulus, neph3 is highly expressed in the developing brain and specific regions of mature midbrain and hindbrain. In line with this, neph3 morphants show aberrant brain morphology. Collectively, the expression of neph3 in glomerulus and brain together with the morphant phenotype imply that neph3 is a pleiotropic gene active during distinct stages of tissue differentiation and associates directly in the regulation of both glomerular and neural development.

Genes / Markers

Marker	Marker Type	Name
cdkn1a	GENE	cyclin dependent kinase inhibitor 1A
kirrel3l	GENE	kirre like nephrin family adhesion molecule 3, like
nphs1	GENE	NPHS1 adhesion molecule, nephrin
nphs2	GENE	NPHS2 stomatin family member, podocin

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Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
kirrel3l	WT	control	Protruding-mouth	brain	ISH	Fig. 1
kirrel3l	WT	control	Prim-5	brain	ISH	Fig. 1
kirrel3l	WT	control	Prim-25	brain	ISH	Fig. 1
kirrel3l	WT	control	Long-pec	cerebellum	ISH	Fig. 2
kirrel3l	WT	control	Day 5	cerebellum	ISH	Fig. 2
kirrel3l	WT	control	Long-pec	hindbrain	ISH	Fig. 2
kirrel3l	WT	control	Day 5	hypothalamus	ISH	Fig. 2
kirrel3l	WT	control	Long-pec	midbrain	ISH	Fig. 2
kirrel3l	WT	control	Day 5	optic tectum	ISH	Fig. 2
kirrel3l	WT	control	Prim-25	pronephric glomerulus	ISH	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-kirrel3l	standard conditions	Long-pec	whole organism increased curvature, abnormal	Fig. 4
WT + MO1-kirrel3l	standard conditions	Day 4	pericardium edematous, abnormal	Fig. 4
WT + MO1-kirrel3l	standard conditions	Day 4	pericardium edematous, abnormal	Fig. 5
WT + MO1-kirrel3l	standard conditions	Day 4	whole organism increased curvature, abnormal	Fig. 4
WT + MO1-kirrel3l	standard conditions	Day 4	whole organism increased curvature, abnormal	Fig. 5
WT + MO1-kirrel3l	standard conditions	Day 6	whole organism increased curvature, abnormal	Fig. 4
WT + MO4-kirrel3l	standard conditions	Prim-5	brain development delayed, abnormal	Fig. 4
WT + MO4-kirrel3l	standard conditions	Prim-5	brain malformed, abnormal	Fig. 4
WT + MO4-kirrel3l	standard conditions	Long-pec	brain development delayed, abnormal	Fig. 4
WT + MO4-kirrel3l	standard conditions	Long-pec	brain malformed, abnormal	Fig. 4

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
kirrel3l	MO1-kirrel3l	MRPHLNO
kirrel3l	MO4-kirrel3l	MRPHLNO

Fish

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Wang et al., 2012 ZDB-PUB-111122-36 PMID:22099175

Neph3 associates with regulation of glomerular and neural development in zebrafish

Wang et al., 2012

ZDB-PUB-111122-36
PMID:22099175