Figure 1621

Ureteric bud cells undergo branching tubulogenesis in three-dimensional extracellular matrix gels. Cell line derived from ureteric bud (UB) and metanephric mesenchyme from day 11.5 mouse embryonic kidney undergo branching tubulogenesis in three-dimensional extracellular matrix gels. Here, UB cells have been induced to form branching tubular structures in response to "conditioned" media collected from the culture of metanephric mesenchymal cells. During normal kidney morphogenesis, these two embryonic cell types undergo a mutually inductive process that ultimately leads to the formation of functional nephrons [74-76]. This model system illustrates this process, ureteric bud cells being induced by factors secreted from metanephric mes-enchymal cells. Thus, this system could represent the simplest in vitro model with the greatest relevance to early kidney development [94]. A, UB cells grown for 1 week in the presence of conditioned media collected from cells cultured from the metanephric mesenchyme. Note the formation of multicellular cords. B, After 2 weeks' growth under the same conditions, UB cells have formed more substantial tubules, now with clear lumens. C, Interestingly, after 2 weeks of culture in a three-dimensional gel composed entirely of growth factor-reduced Matrigel, ureteric bud cells have not formed cords or tubules, only multicellular cysts. Thus, changing the matrix composition can alter the morphology from tubules to cysts, indicating that this model might also be relevant to renal cystic disease, much of which is of developmental origin. (From Sakurai et al. [94]; with permission.)

Free HGF and empty c-Met receptor

HGF binding to c-Met receptor

Dimerization of c-Met receptor and activation of Gab 1

Free HGF and empty c-Met receptor

HGF binding to c-Met receptor

Dimerization of c-Met receptor and activation of Gab 1

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