PUBLICATION

Zebrafish nephrogenesis involves dynamic spatiotemporal expression changes in renal progenitors and essential signals from retinoic acid and irx3b

Authors

Wingert, R.A., and Davidson, A.J.

ID

ZDB-PUB-110719-34

Date

2011

Source

Developmental Dynamics : an official publication of the American Association of Anatomists 240(8): 2011-2027 (Journal)

Registered Authors

Davidson, Alan, Wingert, Rebecca

Keywords

kidney organogenesis, nephron, segmentation, zebrafish

MeSH Terms

Cell Differentiation/physiology
Zebrafish*/anatomy & histology
Zebrafish*/embryology
Zebrafish*/genetics
Stem Cells/cytology
Stem Cells/physiology*
Body Patterning/physiology
Organogenesis/physiology*
Signal Transduction/physiology
Mesoderm/cytology
Mesoderm/physiology
Pronephros/cytology
Pronephros/embryology*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Homeodomain Proteins/genetics
Homeodomain Proteins/metabolism*
Animals
Gene Expression Regulation, Developmental
Transcription Factors/genetics
Transcription Factors/metabolism*
Nephrons/cytology
Nephrons/embryology*
Tretinoin/metabolism*

(all 24)

PubMed

21761484 Full text @ Dev. Dyn.

Abstract

Kidney nephrons are composed of proximal and distal tubule segments that perform unique roles in excretion. The developmental pathways that establish nephron segment identities from renal progenitors are poorly understood. Here, we used the zebrafish pronephros to study nephron segmentation. We found that zebrafish nephron progenitors undergo elaborate spatiotemporal expression changes of many genes before adopting a segment fate. Initially, two domains of nephron progenitors are established, then are subdivided and demarcate individual nephron segments. Using genetic and chemical genetic models of retinoic acid (RA) deficiency, we discovered that RA modulates rostral progenitor formation. To delineate downstream pathways, we knocked down the irx3b transcription factor and found it regulates proximal tubule segment size and distal segment differentiation. Our results suggest a model whereby RA patterns the early field of nephron progenitors, with subsequent factors like irx3b acting to refine later progenitor subdomains and ensure activation of segment-specific gene programs.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
aldh1a2	aldh1a2^nz15/nz15 (TU)	standard conditions	20-25 somites	pronephric duct	ISH	Fig. 4
aldh1a2	aldh1a2^nz15/nz15 (TU)	standard conditions	20-25 somites	segmental plate	ISH	Fig. 4
aldh1a2	WT	standard conditions	20-25 somites	pronephric duct	ISH	Fig. 4
aldh1a2	WT	standard conditions	26+ somites	pronephric duct	ISH	Fig. 6
aldh1a2	WT	standard conditions	26+ somites	pronephros	ISH	Fig. 6
aldh1a2	WT	standard conditions	26+ somites	segmental plate	ISH	Fig. 6
aldh1a2	WT	standard conditions	20-25 somites	segmental plate	ISH	Fig. 4
aldh1a2	WT	standard conditions	5-9 somites	segmental plate	ISH	Fig. 6
aldh1a2	WT	standard conditions	26+ somites	somite	ISH	Fig. 6
aldh1a2	WT	standard conditions	5-9 somites	somite	ISH	Fig. 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
TU + MO1-irx3b + MO2-irx3b	standard conditions	26+ somites	pronephric distal early tubule absent, abnormal	Fig. 7
TU + MO1-irx3b + MO2-irx3b	standard conditions	26+ somites	pronephric duct proximal region increased length, abnormal	Fig. 7
TU + MO4-tbx16	standard conditions	26+ somites	pronephric duct distal region increased length, abnormal	Fig. 6
TU + MO4-tbx16	standard conditions	26+ somites	pronephric duct proximal region decreased length, abnormal	Fig. 6
aldh1a2^i26/+; aldh1a2^nz15/+ (TU)	standard conditions	26+ somites	pronephric duct distal region increased length, abnormal	Fig. 5
aldh1a2^i26/+; aldh1a2^nz15/+ (TU)	standard conditions	26+ somites	pronephric duct proximal region decreased length, abnormal	Fig. 5
aldh1a2^i26/+; aldh1a2^nz15/+ (TU)	standard conditions	Prim-5	otic vesicle decreased distance somite 1, abnormal	Fig. 4
aldh1a2^i26/+; aldh1a2^nz15/+ (TU)	standard conditions	Prim-5	vertebral column anterior region decreased length, abnormal	Fig. 4
aldh1a2^i26/+; aldh1a2^nz15/+ (TU)	standard conditions	Long-pec	head misaligned with trunk, abnormal	Fig. 4
aldh1a2^i26/+; aldh1a2^nz15/+ (TU)	standard conditions	Long-pec	pericardium edematous, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
i26		Point Mutation	aldh1a2
nz15		Point Mutation	aldh1a2

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
irx3b	MO1-irx3b	MRPHLNO
irx3b	MO2-irx3b	MRPHLNO
tbx16	MO4-tbx16	MRPHLNO

Fish

Fish
aldh1a2^i26/i26
aldh1a2^i26/+; aldh1a2^nz15/+ (TU)
aldh1a2^nz15/nz15 + MO1-irx3b + MO2-irx3b (TU)
aldh1a2^nz15/nz15 (TU)
TU
TU + MO1-irx3b + MO2-irx3b
TU + MO4-tbx16
WT
WT + MO4-tbx16

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Entity Type	Entity Symbol	Location
Feature	nz15	Chr: 7 Details
SSLP	z1182	Chr: 7 Details
SSLP	z4999	Chr: 7 Details
SSLP	z8693	Chr: 7 Details
SSLP	z11894	Chr: 7 Details

Wingert et al., 2011 ZDB-PUB-110719-34 PMID:21761484

Zebrafish nephrogenesis involves dynamic spatiotemporal expression changes in renal progenitors and essential signals from retinoic acid and irx3b

Wingert et al., 2011

ZDB-PUB-110719-34
PMID:21761484