Genetic dissection of cadherin function during nephrogenesis

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• R-cadherin expression in the metanephric mesenchyme suggests a role in kidney development.
• Cadherins are cell adhesion molecules critical for tissue morphogenesis.

Purpose of the Study:

• To investigate the role of R-cadherin in kidney development and ontogeny.
• To determine if R-cadherin is essential for embryogenesis.
• To explore potential functional redundancy with other cadherins in kidney development.

Main Methods:

• Generation and analysis of R-cadherin-deficient mice.
• In vivo and in vitro studies of nephrogenesis.
• Morphological and apoptotic analyses of kidney tissues.
• Crossbreeding R-cadherin(-/-) mice with other cadherin knockout strains.

Main Results:

• R-cadherin deficiency did not affect embryogenesis or fertility but resulted in dilated proximal tubules with intracellular vacuoles in adult mice.
• Defects in both ureteric bud-derived and metanephric mesenchyme-derived cells were observed during nephrogenesis.
• Altered morphology, increased apoptosis, and perturbed branching of the ureteric bud epithelium were noted.
• Impaired mesenchymal-epithelial conversion was observed in vitro in R-cadherin(-/-) kidneys.
• Compound knockout mice with other cadherins showed no exacerbated kidney defects, indicating functional redundancy.

Conclusions:

• R-cadherin plays a significant role in the differentiation of both mesenchymal and epithelial components during metanephric kidney development.
• Despite mild kidney defects in its absence, R-cadherin is not essential for embryogenesis.
• Other cadherins may compensate for the loss of R-cadherin, explaining the limited phenotype in single knockout mice.