PUBLICATION

The cdx Genes and Retinoic Acid Control the Positioning and Segmentation of the Zebrafish Pronephros

Authors

Wingert, R.A., Selleck, R., Yu, J., Song, H.D., Chen, Z., Song, A., Zhou, Y., Thisse, B., Thisse, C., McMahon, A.P., and Davidson, A.J.

ID

ZDB-PUB-071029-9

Date

2007

Source

PLoS Genetics 3(10): 1922-1938 (Journal)

Registered Authors

Davidson, Alan, McMahon, Andrew, Song, Anhua, Thisse, Bernard, Thisse, Christine, Wingert, Rebecca, Zhou, Yi

Keywords

Embryos, Somites, Nephrons, Zebrafish, Morphogenic segmentation, Gene expression, In situ hybridization, Kidneys

MeSH Terms

Animals
Cloning, Molecular
Gene Expression Regulation*
Gene Expression Regulation, Developmental*
Homeodomain Proteins/metabolism
In Situ Hybridization
Kidney/embryology*
Mice
Models, Biological
Mutation
Phenotype
Protein Structure, Tertiary
Transcription Factors/metabolism
Tretinoin/metabolism*
Zebrafish

(all 15)

PubMed

17953490 Full text @ PLoS Genet.

Abstract

Kidney function depends on the nephron, which comprises a blood filter, a tubule that is subdivided into functionally distinct segments, and a collecting duct. How these regions arise during development is poorly understood. The zebrafish pronephros consists of two linear nephrons that develop from the intermediate mesoderm along the length of the trunk. Here we show that, contrary to current dogma, these nephrons possess multiple proximal and distal tubule domains that resemble the organization of the mammalian nephron. We examined whether pronephric segmentation is mediated by retinoic acid (RA) and the caudal (cdx) transcription factors, which are known regulators of segmental identity during development. Inhibition of RA signaling resulted in a loss of the proximal segments and an expansion of the distal segments, while exogenous RA treatment induced proximal segment fates at the expense of distal fates. Loss of cdx function caused abrogation of distal segments, a posterior shift in the position of the pronephros, and alterations in the expression boundaries of raldh2 and cyp26a1, which encode enzymes that synthesize and degrade RA, respectively. These results suggest that the cdx genes act to localize the activity of RA along the axis, thereby determining where the pronephros forms. Consistent with this, the pronephric-positioning defect and the loss of distal tubule fate were rescued in embryos doubly-deficient for cdx and RA. These findings reveal a novel link between the RA and cdx pathways and provide a model for how pronephric nephrons are segmented and positioned along the embryonic axis.

Genes / Markers

Marker	Marker Type	Name
aldh1a2	GENE	aldehyde dehydrogenase 1 family, member A2
aqp3a	GENE	aquaporin 3a
cdh17	GENE	cadherin 17, LI cadherin (liver-intestine)
cdx1a	GENE	caudal type homeobox 1a
cdx4	GENE	caudal type homeobox 4
clcnk	GENE	chloride channel K
cyp26a1	GENE	cytochrome P450, family 26, subfamily A, polypeptide 1
dlc	GENE	deltaC
egr2b	GENE	early growth response 2b
gata3	GENE	GATA binding protein 3

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Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
aldh1a2	cdx4^{tv205c/tv205c} + MO2-cdx1a (TU)	standard conditions	10-13 somites		paraxial mesoderm	ISH	Fig. 6
aldh1a2	cdx4^{tv205c/tv205c} + MO2-cdx1a (TU)	standard conditions	5-9 somites		paraxial mesoderm	ISH	Fig. 6
aldh1a2	cdx4^{tv205c/tv205c} + MO2-cdx1a (TU)	standard conditions	10-13 somites		tail bud	ISH	Fig. 6
aldh1a2	cdx4^{tv205c/tv205c} + MO2-cdx1a (TU)	standard conditions	5-9 somites		tail bud	ISH	Fig. 6
aldh1a2	cdx4^{tv205c/tv205c} (TU)	standard conditions	10-13 somites		paraxial mesoderm	ISH	Fig. 6
aldh1a2	cdx4^{tv205c/tv205c} (TU)	standard conditions	5-9 somites		paraxial mesoderm	ISH	Fig. 6
aldh1a2	TU	standard conditions	10-13 somites		paraxial mesoderm	ISH	Fig. 6
aldh1a2	TU	standard conditions	5-9 somites		paraxial mesoderm	ISH	Fig. 6
aqp3a	cdx4^{tv205c/tv205c} + MO2-cdx1a (TU)	standard conditions	Prim-5	Not Detected	cloacal chamber	ISH	Fig. 5
aqp3a	cdx4^{tv205c/tv205c} (TU)	standard conditions	Prim-5	Not Detected	cloacal chamber	ISH	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	corpuscles of Stannius increased amount, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	corpuscles of Stannius increased size, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	podocyte aplastic, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	pronephric distal late tubule increased length, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	pronephric proximal convoluted tubule aplastic, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	pronephric proximal straight tubule aplastic, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	pronephric tubule aplastic, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	corpuscles of Stannius increased amount, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	corpuscles of Stannius increased size, abnormal	Fig. 3
TU	chemical treatment: 4-(diethylamino)benzaldehyde	Long-pec	podocyte aplastic, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
tv205c		Small Deletion	cdx4

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
aldh1a2	MO3-aldh1a2	MRPHLNO
cdx1a	MO2-cdx1a	MRPHLNO

Fish

Fish
cdx4^{tv205c/tv205c} + MO2-cdx1a (TU)
cdx4^{tv205c/tv205c} (TU)
TL
TU
TU + MO3-aldh1a2
WT

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Wingert et al., 2007 ZDB-PUB-071029-9 PMID:17953490

The cdx Genes and Retinoic Acid Control the Positioning and Segmentation of the Zebrafish Pronephros

Wingert et al., 2007

ZDB-PUB-071029-9
PMID:17953490