title: Partitioning-Defective 1a/b Depletion Impairs Glomerular and Proximal Tubule Development.
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, and Notch effecter Hes1. Together, these data demonstrate that Par1a/b has a key role in glomerular and proximal tubule development, likely via modulation of Notch signaling.
authors.affiliation: Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, New York.
authors.forename: Oleh
authors.initials: O
authors.lastname: Akchurin
authors.affiliation: Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, New York.
authors.forename: Zhongfang
authors.initials: Z
authors.lastname: Du
authors.affiliation: Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, New York.
authors.forename: Nadira
authors.initials: N
authors.lastname: Ramkellawan
authors.affiliation: Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, New York.
authors.forename: Vidhi
authors.initials: V
authors.lastname: Dalal
authors.affiliation: Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Han
authors.affiliation: Department of Pathology, Montefiore Medical Center, Bronx, New York; and.
authors.forename: James
authors.initials: J
authors.lastname: Pullman
authors.affiliation: Department of Development and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Anne
authors.initials: A
authors.lastname: Müsch
authors.affiliation: Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
authors.affiliation: Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, New York; kreidy@montefiore.org.|Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Reidy
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D007678:Kidney Glomerulus / Q000254:growth & development*; D007684:Kidney Tubules / Q000254:growth & development*; D051379:Mice; D038081:Organogenesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C122043:Mark2 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: cell adhesion; kidney development; podocyte; proximal tubule; renal epithelial cell; ureteric bud