Organ In Vitro Culture: What Have We Learned about Early Kidney Development?

Figure 3

Schematic of kidney development: (a) MM influence UB outgrowth from the Wolffian duct. Genes, such as Osr1, Wt1, Pax2, and Sall1, upregulate GDNF production. GDNF is secreted from the MM and binds to Ret receptors and induces budding of the ureteric bud. The ectopic bud outgrowth is prevented by the BMP4 that surrounds Wolffian duct. Slit2 and Robo2 action reduce GDNF production in the anterior part on the MM. (b) Once the UB invades the MM, its branching is regulated by HGF, FGF, GDNF, and EGF inductive action on Ret, while Semaphorin 3A is downregulating the UB branching (left side). At the tip of the UB, the MM condenses and forms heterogenic cell population with expression of CITED1, Six2, and Wnt4. Upon Wnt9b action, Wnt4 induced nephron formation by comma- and S-shape body formation. MET takes place. (c) Distal nephron development depends on ROCK signalling, while proximal nephron—glomeruli development depends on Notch2 signalling. (d) Microphotographs of kidney rudiments developing in vitro, presenting all main stages of nephron formation.

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