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Midline signaling regulates kidney positioning but not nephrogenesis through Shh
- Source :
- Developmental Biology. (2):518-527
- Publisher :
- Elsevier Inc.
-
Abstract
- The role of axial structures, especially the notochord, in metanephric kidney development has not been directly examined. Here, we showed that disruption of the notochord and floor plate by diphtheria toxin (DTA)-mediated cell ablation did not disrupt nephrogenesis, but resulted in kidney fusions, resembling horseshoe kidneys in humans. Axial disruptions led to more medially positioned metanephric mesenchyme (MM) in midgestation. However, neither axial disruption nor the ensuing positional shift of the MM affected the formation of nephrons and other structures within the kidney. Response to Shh signaling was greatly reduced in midline cell populations in the mutants. To further ascertain the molecular mechanism underlying these abnormalities, we specifically inactivated Shh in the notochord and floor plate. We found that depleting the axial source of Shh was sufficient to cause kidney fusion, even in the presence of the notochord. These results suggested that the notochord is dispensable for nephrogenesis but required for the correct positioning of the metanephric kidney. Axial Shh signal appears to be critical in conferring the effects of axial structures on kidney positioning along the mediolateral axis. These studies also provide insights into the pathogenesis of horseshoe kidneys and how congenital kidney defects can be caused by signals outside the renal primordia.
- Subjects :
- Horseshoe kidney
Kidney development
Kidney
Mediolateral positioning
Mesoderm
Mice
0302 clinical medicine
Intermediate mesoderm
Wolffian duct
Transgenes
Sonic hedgehog
In Situ Hybridization
0303 health sciences
Ureteric bud
Gene Expression Regulation, Developmental
Anatomy
Immunohistochemistry
medicine.anatomical_structure
Sonic Hedgehog
embryonic structures
Signal Transduction
animal structures
Notochord
Mammalian embryology
Embryonic Development
Mice, Transgenic
Biology
Models, Biological
Article
03 medical and health sciences
medicine
Animals
Hedgehog Proteins
Molecular Biology
030304 developmental biology
Floor plate
Body Patterning
Metanephric mesenchyme
urogenital system
Cell Biology
medicine.disease
Embryo, Mammalian
Animals, Newborn
Mutation
biology.protein
Diphtheria toxin
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 00121606
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....bb7934a8a348d2d423435e90e5e292c7
- Full Text :
- https://doi.org/10.1016/j.ydbio.2010.02.007