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Semaphorins in kidney development and disease: modulators of ureteric bud branching, vascular morphogenesis, and podocyte-endothelial crosstalk

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Abstract

Semaphorins are guidance proteins that play important roles in organogenesis and disease. Expression of class 3 semaphorins and their receptors is regulated during kidney development. Gain- and loss-of-function experiments demonstrated that tight semaphorin3a gene dosage is required for podocyte differentiation, and for the establishment of a normal glomerular filtration barrier. Sema3a modulates kidney vascular patterning acting as a negative regulator of endothelial cell migration and survival. Excess podocyte semaphorin3a expression causes glomerular disease in mice. In addition, Sema3a is a negative regulator of ureteric bud branching, whereas Sema3c is a positive regulator of ureteric bud and endothelial cell branching morphogenesis. In summary, secreted semaphorins modulate ureteric bud branching, vascular patterning, and podocyte-endothelial crosstalk, suggesting that they play a role in renal disease. Understanding the signaling pathways downstream from semaphorin receptors will provide insight into the mechanism of action of semaphorins in renal pathology.

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Acknowledgements

This study was supported by NIH RO1-DK64187 and DK59333 (A.T.), K.R. was supported by NIH training grant T32 DK-007110. We thank K. Susztak (Albert Einstein College of Medicine) for providing the RNA samples from PAN rats and Db/Db mice.

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Authors and Affiliations

  1. Yale University School of Medicine, 333 Cedar Avenue, New Haven, CT, 06520, USA

    Alda Tufro

  2. Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA

    Kimberly Reidy

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  1. Kimberly Reidy
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  2. Alda Tufro
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Correspondence to Alda Tufro.

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Reidy, K., Tufro, A. Semaphorins in kidney development and disease: modulators of ureteric bud branching, vascular morphogenesis, and podocyte-endothelial crosstalk. Pediatr Nephrol 26, 1407–1412 (2011). https://doi.org/10.1007/s00467-011-1769-1

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  • DOI: https://doi.org/10.1007/s00467-011-1769-1

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