The development of the mammalian kidney begins when the ureteric bud invades undifferentiated mesenchyme. These two embryonic structures engage in reciprocal induction mediated by multiple growth factors and extracellular signals. These signals are not yet well defined, but growth factors that modulate the expression and composition of the extracellular matrix and its cell-surface receptors are clearly implicated in the process of tubulogenesis. Preliminary work in the Sponsor's laboratory has identified several intriguing growth factors and cell-surface receptors. Specifically, the dystroglycan complex, an epithelial cell-surface glycoprotein receptor for laminin, has been shown to be significantly up- regulated by factors derived from embryonic mesenchyme. Using methods developed in the Sponsor's lab, including novel 3- dimensional cell culture techniques, the role of dystroglycan in branching morphogenesis will be studied. These investigations will provide valuable insight into the inductive mechanisms regulating tubule formation and epithelial differentiation. Furthermore, they will provide the applicant with a broad background in the molecular biology of renal development and will train the applicant to be an independent investigator in the field.
| Bush, Kevin T; Sakurai, Hiroyuki; Steer, Dylan L et al. (2004) TGF-beta superfamily members modulate growth, branching, shaping, and patterning of the ureteric bud. Dev Biol 266:285-98 |
| Steer, Dylan L; Shah, Mita M; Bush, Kevin T et al. (2004) Regulation of ureteric bud branching morphogenesis by sulfated proteoglycans in the developing kidney. Dev Biol 272:310-27 |
| Steer, Dylan L; Bush, Kevin T; Meyer, Tobias N et al. (2002) A strategy for in vitro propagation of rat nephrons. Kidney Int 62:1958-65 |
| Qiao, J; Bush, K T; Steer, D L et al. (2001) Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech Dev 109:123-35 |
| Slatopolsky, E; Delmez, J A (1996) Pathogenesis of secondary hyperparathyroidism. Nephrol Dial Transplant 11 Suppl 3:130-5 |
