This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dahl, U.
Right arrow Articles by Semb, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dahl, U.
Right arrow Articles by Semb, H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2002, p. 1474-1487, Vol. 22, No. 5
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.5.1474-1487.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Genetic Dissection of Cadherin Function during Nephrogenesis

Ulf Dahl,1 Anders Sjödin,1 Lionel Larue,2 Glenn L. Radice,3 Stefan Cajander,4 Masatoshi Takeichi,5 Rolf Kemler,6 and Henrik Semb1*

Department of Medical Biochemistry, Göteborg University, S-405 30 Göteborg,1 Department of Pathology, Umeå University, S-901 87 Umeå, Sweden,4 Genetique du Developpement des Melanocytes Institut Curie, Section Recherche UMR146 CNRS, Centre Universitaire, 91405 Orsay, France,2 Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104,3 Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan,5 Max-Planck Institut für Immunbiologie, D-79108 Freiburg, Germany6

Received 11 July 2001/ Returned for modification 14 August 2001/ Accepted 6 December 2001

The distinct expression of R-cadherin in the induced aggregating metanephric mesenchyme suggests that it may regulate the mesenchymal-epithelial transition during kidney development. To address whether R-cadherin is required for kidney ontogeny, R-cadherin-deficient mice were generated. These mice appeared to be healthy and were fertile, demonstrating that R-cadherin is not essential for embryogenesis. The only kidney phenotype of adult mutant animals was the appearance of dilated proximal tubules, which was associated with an accumulation of large intracellular vacuoles. Morphological analysis of nephrogenesis in R-cadherin-/- mice in vivo and in vitro revealed defects in the development of both ureteric bud-derived cells and metanephric mesenchyme-derived cells. First, the morphology and organization of the proximal parts of the ureteric bud epithelium were altered. Interestingly, these morphological changes correlated with an increased rate of apoptosis and were further supported by perturbed branching and patterning of the ureteric bud epithelium during in vitro differentiation. Second, during in vitro studies of mesenchymal-epithelial conversion, significantly fewer epithelial structures developed from R-cadherin-/- kidneys than from wild-type kidneys. These data suggest that R-cadherin is functionally involved in the differentiation of both mesenchymal and epithelial components during metanephric kidney development. Finally, to investigate whether the redundant expression of other classic cadherins expressed in the kidney could explain the rather mild kidney defects in R-cadherin-deficient mice, we intercrossed R-cadherin-/- mice with cadherin-6-/-, P-cadherin-/-, and N-cadherin+/- mice. Surprisingly, however, in none of the compound knockout strains was kidney development affected to a greater extent than within the individual cadherin knockout strains.

* Corresponding author. Mailing address: Department of Medical Biochemistry, Göteborg University, S-405 30 Göteborg, Sweden. Phone: 46 31 773 3779. Fax: 46 31 41 61 08. E-mail: Henril.Semb{at}medkem.gu.se

Molecular and Cellular Biology, March 2002, p. 1474-1487, Vol. 22, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.5.1474-1487.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Stepniak, E., Radice, G. L., Vasioukhin, V. (2009). Adhesive and Signaling Functions of Cadherins and Catenins in Vertebrate Development. Cold Spring Harb. Perspect. Biol. 1: a002949-a002949 [Abstract] [Full Text]  
  • Schluter, M. A., Margolis, B. (2009). Apical Lumen Formation in Renal Epithelia. J. Am. Soc. Nephrol. 20: 1444-1452 [Abstract] [Full Text]  
  • Agiostratidou, G., Li, M., Suyama, K., Badano, I., Keren, R., Chung, S., Anzovino, A., Hulit, J., Qian, B., Bouzahzah, B., Eugenin, E., Loudig, O., Phillips, G. R., Locker, J., Hazan, R. B. (2009). Loss of Retinal Cadherin Facilitates Mammary Tumor Progression and Metastasis. Cancer Res. 69: 5030-5038 [Abstract] [Full Text]  
  • Bathula, C. S., Garrett, S. H., Zhou, X. D., Sens, M. A., Sens, D. A., Somji, S. (2008). Cadmium, Vectorial Active Transport, and MT-3-Dependent Regulation of Cadherin Expression in Human Proximal Tubular Cells. Toxicol Sci 102: 310-318 [Abstract] [Full Text]  
  • Wheelock, M. J., Shintani, Y., Maeda, M., Fukumoto, Y., Johnson, K. R. (2008). Cadherin switching. J. Cell Sci. 121: 727-735 [Abstract] [Full Text]  
  • Arciniegas, E., Frid, M. G., Douglas, I. S., Stenmark, K. R. (2007). Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L1-L8 [Abstract] [Full Text]  
  • Park, J.-S., Valerius, M. T., McMahon, A. P. (2007). Wnt/{beta}-catenin signaling regulates nephron induction during mouse kidney development. Development 134: 2533-2539 [Abstract] [Full Text]  
  • Boyle, S., de Caestecker, M. (2006). Role of transcriptional networks in coordinating early events during kidney development. Am. J. Physiol. Renal Physiol. 291: F1-F8 [Abstract] [Full Text]  
  • Covington, M. D., Bayless, K. J., Burghardt, R. C., Davis, G. E., Parrish, A. R. (2005). Ischemia-induced cleavage of cadherins in NRK cells: evidence for a role of metalloproteinases. Am. J. Physiol. Renal Physiol. 289: F280-F288 [Abstract] [Full Text]  
  • Krauss, R. S., Cole, F., Gaio, U., Takaesu, G., Zhang, W., Kang, J.-S. (2005). Close encounters: regulation of vertebrate skeletal myogenesis by cell-cell contact. J. Cell Sci. 118: 2355-2362 [Abstract] [Full Text]  
  • Ward, R. D., Raetzman, L. T., Suh, H., Stone, B. M., Nasonkin, I. O., Camper, S. A. (2005). Role of PROP1 in Pituitary Gland Growth. Mol. Endocrinol. 19: 698-710 [Abstract] [Full Text]  
  • Fan, H., Harrell, J. R., Dipp, S., Saifudeen, Z., El-Dahr, S. S. (2005). A novel pathological role of p53 in kidney development revealed by gene-environment interactions. Am. J. Physiol. Renal Physiol. 288: F98-F107 [Abstract] [Full Text]  
  • Miotto, E., Sabbioni, S., Veronese, A., Calin, G. A., Gullini, S., Liboni, A., Gramantieri, L., Bolondi, L., Ferrazzi, E., Gafa, R., Lanza, G., Negrini, M. (2004). Frequent Aberrant Methylation of the CDH4 Gene Promoter in Human Colorectal and Gastric Cancer. Cancer Res. 64: 8156-8159 [Abstract] [Full Text]  
  • Jiang, J., Dean, D., Burghardt, R. C., Parrish, A. R. (2004). Disruption of Cadherin/Catenin Expression, Localization, and Interactions During HgCl2-Induced Nephrotoxicity. Toxicol Sci 80: 170-182 [Abstract] [Full Text]  
  • Roitbak, T., Ward, C. J., Harris, P. C., Bacallao, R., Ness, S. A., Wandinger-Ness, A. (2004). A Polycystin-1 Multiprotein Complex Is Disrupted in Polycystic Kidney Disease Cells. Mol. Biol. Cell 15: 1334-1346 [Abstract] [Full Text]  
  • Kanwar, Y. S., Wada, J., Lin, S., Danesh, F. R., Chugh, S. S., Yang, Q., Banerjee, T., Lomasney, J. W. (2004). Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis. Am. J. Physiol. Renal Physiol. 286: F202-F215 [Abstract] [Full Text]  
  • Wang, P., Pereira, F. A., Beasley, D., Zheng, H. (2003). Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis. Development 130: 5019-5029 [Abstract] [Full Text]  
  • Fagman, H., Grande, M., Edsbagge, J., Semb, H., Nilsson, M. (2003). Expression of Classical Cadherins in Thyroid Development: Maintenance of an Epithelial Phenotype throughout Organogenesis. Endocrinology 144: 3618-3624 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»