Journal article
Vitamin A controls epithelial/mesenchymal interactions through Ret expression
Nature genetics, Vol.27(1), pp.74-78
01/2001
DOI: 10.1038/83792
PMID: 11138002
Abstract
Mutations or rearrangements in the gene encoding the receptor tyrosine kinase RET result in Hirschsprung disease, cancer and renal malformations. The standard model of renal development involves reciprocal signaling between the ureteric bud epithelium, inducing metanephric mesenchyme to differentiate into nephrons, and metanephric mesenchyme, inducing the ureteric bud to grow and branch. RET and GDNF (a RET ligand) are essential mediators of these epithelial-mesenchymal interactions. Vitamin A deficiency has been associated with widespread embryonic abnormalities, including renal malformations. The vitamin A signal is transduced by nuclear retinoic acid receptors (RARs). We previously showed that two RAR genes, Rara and Rarb2, were colocalized in stromal mesenchyme, a third renal cell type, where their deletion led to altered stromal cell patterning, impaired ureteric bud growth and downregulation of Ret in the ureteric bud. Here we demonstrate that forced expression of Ret in mice deficient for both Rara and Rarb2 (Rara−/−Rarb2−/−) genetically rescues renal development, restoring ureteric bud growth and stromal cell patterning. Our studies indicate the presence of a new reciprocal signaling loop between the ureteric bud epithelium and the stromal mesenchyme, dependent on Ret and vitamin A. In the first part of the loop, vitamin-A-dependent signals secreted by stromal cells control Ret expression in the ureteric bud. In the second part of the loop, ureteric bud signals dependent on Ret control stromal cell patterning.
Details
- Title: Subtitle
- Vitamin A controls epithelial/mesenchymal interactions through Ret expression
- Creators
- Cathy Mendelsohn - Department of Urology, Columbia UniversityMichael Shy - Department of Urology, Columbia UniversityFrank Costantini - Department of Genetics & Development, Columbia UniversitySuzanna Gim - Department of Urology, Columbia UniversityMargaret Clagett-Dame - Department of Biochemistry and Pharmaceutical Sciences, University of Wisconsin-MadisonNatalie Bello - Department of Urology, Columbia UniversityShankar Srinivas - Department of Genetics & Development, Columbia UniversityEkatherina Batourina - Department of Urology, Columbia University
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.27(1), pp.74-78
- DOI
- 10.1038/83792
- PMID
- 11138002
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English
- Date published
- 01/2001
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020656802771
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