TY - JOUR
T1 - Partitioning-defective 1a/b depletion impairs glomerular and proximal tubule development
AU - Akchurin, Oleh
AU - Du, Zhongfang
AU - Ramkellawan, Nadira
AU - Dalal, Vidhi
AU - Han, Seung Hyeok
AU - Pullman, James
AU - Müsch, Anne
AU - Susztak, Katalin
AU - Reidy, Kimberly J.
N1 - Publisher Copyright:
Copyright © 2016 by the American Society of Nephrology.
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2014111124
DO - 10.1681/ASN.2014111124
M3 - Article
C2 - 27185860
AN - SCOPUS:85021664020
SN - 1046-6673
VL - 27
SP - 3725
EP - 3737
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 12
ER -