title: Renal collecting system growth and function depend upon embryonic γ1 laminin expression.
abstract: In order to understand the functions of laminins in the renal collecting system, the Lamc1 gene was inactivated in the developing mouse ureteric bud (UB). Embryos bearing null alleles exhibited laminin deficiency prior to mesenchymal tubular induction and either failed to develop a UB with involution of the mesenchyme, or developed small kidneys with decreased proliferation and branching, delayed renal vesicle formation and postnatal emergence of a water transport deficit. Embryonic day 12.5 kidneys revealed an almost complete absence of basement membrane proteins and reduced levels of α6 integrin and FGF2. mRNA levels for fibroblast growth factor 2 (FGF2) and mediators of the GDNF/RET and WNT11 signaling pathway were also decreased. Furthermore, collecting duct cells derived from laminin-deficient kidneys and grown in collagen gels were found to proliferate and branch slowly. The laminin-deficient cells exhibited decreased activation of growth factor- and integrin-dependent pathways, whereas heparin lyase-treated and β1 integrin-null cells exhibited more selective decreases. Collectively, these data support a requirement of γ1 laminins for assembly of the collecting duct system basement membrane, in which immobilized ligands act as solid-phase agonists to promote branching morphogenesis, growth and water transport functions.
authors: Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors: Dong-Hua
authors: DH
authors: Yang
authors: Karen K
authors: KK
authors: McKee
authors: Zu-Lin
authors: ZL
authors: Chen
authors: Glenda
authors: G
authors: Mernaugh
authors: Sidney
authors: S
authors: Strickland
authors: Roy
authors: R
authors: Zent
authors: Peter D
authors: PD
authors: Yurchenco
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000196:embryology / Q000378:metabolism; D003919:Diabetes Insipidus / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006133:Growth Substances / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006869:Hydronephrosis / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*; D007797:Laminin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D011247:Pregnancy; D015398:Signal Transduction
chemical_list: D006133:Growth Substances; D006497:Heparan Sulfate; D019012:Integrin beta1; D007797:Laminin; C089141:laminin gamma 1