Partitioning-defective 1a/b depletion impairs glomerular and proximal tubule development

Oleh Akchurin, Zhongfang Du, Nadira Ramkellawan, Vidhi Dalal, Seung Hyeok Han, James Pullman, Anne Müsch, Katalin Susztak, Kimberly J. Reidy

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Abstract

The kidney is a highly polarized epithelial organ that develops from undifferentiated mesenchyme, although the mechanisms that regulate the development of renal epithelial polarity are incompletely understood. Partitioning-defective 1 (Par1) proteins have been implicated in cell polarity and epithelial morphogenesis; however, the role of these proteins in the developing kidney has not been established. Therefore,we studied the contribution of Par1a/b to renal epithelial development. We examined the renal phenotype of newborn compound mutant mice carrying only one allele of Par1a or Par1b. Loss of three out of four Par1a/b alleles resulted in severe renal hypoplasia, associated with impaired ureteric bud branching. Compared with kidneys of newborn control littermates, kidneys of newborn mutant mice exhibited dilated proximal tubules and immature glomeruli, and the renal proximal tubular epithelia lacked proper localization of adhesion complexes. Furthermore, Par1a/b mutants expressed low levels of renal Notch ligand Jag1, activated Notch2, andNotch effecterHes1. Together, these data demonstrate that Par1a/b has a key role in glomerular and proximal tubule development, likely via modulation of Notch signaling.

Original languageEnglish
Pages (from-to)3725-3737
Number of pages13
JournalJournal of the American Society of Nephrology
Volume27
Issue number12
DOIs
Publication statusPublished - 2016 Dec

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All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Akchurin, O., Du, Z., Ramkellawan, N., Dalal, V., Han, S. H., Pullman, J., Müsch, A., Susztak, K., & Reidy, K. J. (2016). Partitioning-defective 1a/b depletion impairs glomerular and proximal tubule development. Journal of the American Society of Nephrology, 27(12), 3725-3737. https://doi.org/10.1681/ASN.2014111124