title: p120 catenin is required for normal renal tubulogenesis and glomerulogenesis.
abstract: Defects in the development or maintenance of tubule diameter correlate with polycystic kidney disease. Here, we report that absence of the cadherin regulator p120 catenin (p120ctn) from the renal mesenchyme prior to tubule formation leads to decreased cadherin levels with abnormal morphologies of early tubule structures and developing glomeruli. In addition, mutant mice develop cystic kidney disease, with markedly increased tubule diameter and cellular proliferation, and detached luminal cells only in proximal tubules. The p120ctn homolog Arvcf is specifically absent from embryonic proximal tubules, consistent with the specificity of the proximal tubular phenotype. p120ctn knockdown in renal epithelial cells in 3D culture results in a similar cystic phenotype with reduced levels of E-cadherin and active RhoA. We find that E-cadherin knockdown, but not RhoA inhibition, phenocopies p120ctn knockdown. Taken together, our data show that p120ctn is required for early tubule and glomerular morphogenesis, as well as control of luminal diameter, probably through regulation of cadherins.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA 94158, USA. denise.marciano@utsouthwestern.edu
authors.forename: Denise K
authors.initials: DK
authors.lastname: Marciano
authors.forename: Paul R
authors.initials: PR
authors.lastname: Brakeman
authors.forename: Chao-Zong
authors.initials: CZ
authors.lastname: Lee
authors.forename: Natalie
authors.initials: N
authors.lastname: Spivak
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Eastburn
authors.forename: David M
authors.initials: DM
authors.lastname: Bryant
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Beaudoin
authors.forename: Ilse
authors.initials: I
authors.lastname: Hofmann
authors.forename: Keith E
authors.initials: KE
authors.lastname: Mostov
authors.forename: Louis F
authors.initials: LF
authors.lastname: Reichardt
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051177:Catenins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D005260:Female; D055785:Gene Knockdown Techniques; D052177:Kidney Diseases, Cystic / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000196:embryology* / Q000378:metabolism*; D007684:Kidney Tubules / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009024:Morphogenesis; D009399:Nephrons / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin
chemical_list: D051186:Armadillo Domain Proteins; C485846:Arvcf protein, mouse; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin