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PMID:15634693

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Citation

Levinson, RS, Batourina, E, Choi, C, Vorontchikhina, M, Kitajewski, J and Mendelsohn, CL (2005) Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development 132:529-39

Abstract

Development of the metanephric kidney involves the establishment of discrete zones of induction and differentiation that are crucial to the future radial patterning of the organ. Genetic deletion of the forkhead transcription factor, Foxd1, results in striking renal abnormalities, including the loss of these discrete zones and pelvic fused kidneys. We have investigated the molecular and cellular basis of the kidney phenotypes displayed by Foxd1-null embryos and report here that they are likely to be caused by a failure in the correct formation of the renal capsule. Unlike the single layer of Foxd1-positive stroma that comprises the normal renal capsule, the mutant capsule contains heterogeneous layers of cells, including Bmp4-expressing cells, which induce ectopic phospho-Smad1 signaling in nephron progenitors. This missignaling disrupts their early patterning, which, in turn, causes mispatterning of the ureteric tree, while delaying and disorganizing nephrogenesis. In addition, the defects in capsule formation prevent the kidneys from detaching from the body wall, thus explaining their fusion and pelvic location. For the first time, functions have been ascribed to the renal capsule that include delineation of the organ and acting as a barrier to inappropriate exogenous signals, while providing a source of endogenous signals that are crucial to the establishment of the correct zones of induction and differentiation.

Links

PubMed Online version:10.1242/dev.01604

Keywords

Animals; Body Patterning/genetics; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins/metabolism; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Heterozygote; Kidney/cytology; Kidney/embryology; Kidney/metabolism; Mesoderm/cytology; Mesoderm/metabolism; Mice; Mice, Knockout; Mutation/genetics; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Signal Transduction; Ureter/metabolism; Ureter/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BMP4

involved_in

GO:0090191: negative regulation of branching involved in ureteric bud morphogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0030513: positive regulation of BMP signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0060678: dichotomous subdivision of terminal units involved in ureteric bud branching

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0072076: nephrogenic mesenchyme development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0072210: metanephric nephron development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0072213: metanephric capsule development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0072267: metanephric capsule specification

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0090184: positive regulation of kidney development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXD1

involved_in

GO:0072268: pattern specification involved in metanephros development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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