PUBLICATION

Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros

Authors

Liu, Y., Pathak, N., Kramer-Zucker, A., and Drummond, I.A.

ID

ZDB-PUB-070212-38

Date

2007

Source

Development (Cambridge, England) 134(6): 1111-1122 (Journal)

Registered Authors

Drummond, Iain, Kramer-Zucker, Albrecht, Liu, Yan

Keywords

Pronephros, Jagged 2, Multiciliated cell, Notch3, double bubble, mind bomb, Zebrafish

MeSH Terms

Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/metabolism
Ubiquitin-Protein Ligases/genetics
Ubiquitin-Protein Ligases/metabolism
Receptors, Notch/genetics
Receptors, Notch/physiology*
Embryo, Nonmammalian/cytology
Embryo, Nonmammalian/metabolism
Homeodomain Proteins/genetics
Homeodomain Proteins/metabolism*
Animals
Signal Transduction
Cilia/metabolism
Cilia/physiology
Epithelium/metabolism
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism*
Nephrons/cytology
Nephrons/embryology*
Nephrons/metabolism
Receptor, Notch1/genetics
Receptor, Notch1/metabolism*
Cell Differentiation
Zebrafish Proteins/antagonists & inhibitors
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Zebrafish Proteins/physiology*
Amyloid Precursor Protein Secretases/antagonists & inhibitors
Amyloid Precursor Protein Secretases/metabolism
Calcium-Binding Proteins/antagonists & inhibitors
Calcium-Binding Proteins/genetics
Calcium-Binding Proteins/metabolism

(all 33)

PubMed

17287248 Full text @ Development

Abstract

Epithelial tubules consist of multiple cell types that are specialized for specific aspects of organ function. In the zebrafish pronephros, multiciliated cells (MCCs) are specialized for fluid propulsion, whereas transporting epithelial cells recover filtered-blood solutes. These cell types are distributed in a 'salt-and-pepper' fashion in the pronephros, suggesting that a lateral inhibition mechanism may play a role in their differentiation. We find that the Notch ligand Jagged 2 is expressed in MCCs and that notch3 is expressed in pronephric epithelial cells. Morpholino knockdown of either jagged 2 or notch3, or mutation in mind bomb (in which Notch signaling is impaired), dramatically expands ciliogenic gene expression, whereas ion transporter expression is lost, indicating that pronephric cells are transfated to MCCs. Conversely, ectopic expression of the Notch1a intracellular domain represses MCC differentiation. Gamma-secretase inhibition using DAPT demonstrated a requirement for Notch signaling early in pronephric development, before the pattern of MCC differentiation is apparent. Strikingly, we find that jagged 2 knockdown generates extra cilia and is sufficient to rescue the kidney cilia mutant double bubble. Our results indicate that Jagged 2/Notch signaling modulates the number of multiciliated versus transporting epithelial cells in the pronephros by way of a genetic pathway involving repression of rfx2, a key transcriptional regulator of the ciliogenesis program.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
kca3Tg/+; kca4Tg/+	heat shock	Prim-15	pronephros	ISH	Fig. 8
kca3Tg/+; kca4Tg/+	heat shock	Prim-15	pronephros	ISH	Fig. 8
mib1^m132/m132 (AB)	standard conditions	Prim-15	pronephros	ISH	Fig. 7
WT	chemical treatment: DAPT	Prim-15	pronephros	ISH	Fig. 8
WT	control	Prim-15	pronephros	ISH	Fig. 8
WT	standard conditions	Prim-15	pronephros	ISH	Fig. 7
WT	standard conditions	Prim-15	pronephros	ISH	Fig. 3
WT	standard conditions	Prim-15	pronephros	ISH	Fig. 2
WT	control	Prim-15	pronephros	ISH	Fig. 5
WT	standard conditions	High-pec	pronephros	ISH	Fig. 4

1 - 10 of 66

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: DAPT	Prim-15	cell differentiation involved in pronephros development disrupted, abnormal	Fig. 8
WT	chemical treatment: DAPT	Prim-15	pronephros multi-ciliated epithelial cell increased amount, abnormal	Fig. 8
WT + MO1-jag2b	standard conditions	Prim-15	cell differentiation involved in pronephros development disrupted, abnormal	Fig. 5
WT + MO1-jag2b	standard conditions	Prim-15	pronephros multi-ciliated epithelial cell increased amount, abnormal	Fig. 5
WT + MO4-jag2b	standard conditions	Prim-15	cell differentiation involved in pronephros development disrupted, abnormal	Fig. 5
WT + MO4-jag2b	standard conditions	Prim-15	pronephros multi-ciliated epithelial cell increased amount, abnormal	Fig. 5
WT + MO4-jag2b	standard conditions	Pec-fin	cilium assembly increased occurrence, abnormal	Fig. 10
WT + MO4-jag2b	standard conditions	Pec-fin	pronephros cilium increased amount, abnormal	Fig. 10
WT + MO4-notch3	standard conditions	Prim-15	cell differentiation involved in pronephros development disrupted, abnormal	Fig. 6
WT + MO4-notch3	standard conditions	Prim-15	pronephros cellular quality, abnormal	Fig. 6

1 - 10 of 27

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
kca3Tg	Tg(5xUAS-E1B:6xMYC-notch1a)	Transgenic Insertion
kca4Tg	Tg(-1.5hsp70l:GAL4)	Transgenic Insertion
m132		Point Mutation	mib1
m468		Unknown	dbl
zf34Tg	Tg(atp1a1a.4:EGFP)	Transgenic Insertion

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
jag1b	MO1-jag1b	MRPHLNO
jag2b	MO1-jag2b	MRPHLNO
jag2b	MO4-jag2b	MRPHLNO
notch3	MO4-notch3	MRPHLNO
rfx2	MO1-rfx2	MRPHLNO

Fish

Fish
dbl^m468/m468
dbl^m468/m468
dbl^m468/m468 + MO4-jag2b
dbl^m468/+
kca3Tg/+; kca4Tg/+
mib1^m132/m132 (AB)
WT
WT + MO1-jag2b
WT + MO1-jag2b + MO4-jag2b
WT + MO4-jag2b

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4	EFG	GAL4

Mapping

Liu et al., 2007 ZDB-PUB-070212-38 PMID:17287248

Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros

Liu et al., 2007

ZDB-PUB-070212-38
PMID:17287248