n identified that contribute to the patterning and timing of ureteric bud development via Gdnf control. Fgf antagonism by Sprouty controls the sensitivity of the ureteric bud to Gdnf via an Fgf10-dependent mechanism, and signals from the Bmp family are also involved in the initiation of ureteric bud development, although two of them, Bmp2 1 November 2011 | Volume 6 | Issue 11 15516710” | e27676 Cer1 and Ureteric Bud Branching and Bmp4, are considered to act as inhibitors of the process. Much less is known about the mechanisms that control the later steps in ureteric bud branching, i.e. the establishment of the complex spatial organization of the ureteric tree, which represents the future collecting duct system. Gdnf/Ret appears to have some role, and this together with Wnt11 exerts a positive feedback effect on early ureteric bud development. The mode of action of the Bmps is regulated by a panel of extracellular anti-Bmp and pro-Bmp activity factors such as Crossveinless2, representing a Bmp agonist in the developing kidney. The Cerberus/Dan family forms one group of secreted ” Bmp antagonists that includes the mCerberus 1 homologue, Prdc, Dan, Drm, Sost/Ectodin/Wise/USAG1 and Dte proteins. Gremlin advances early ureteric bud formation by antagonising Bmp4/Bmp7 signalling, while USAG1 may serve as a Bmp7 antagonist in the more advanced kidney. Cerberus encodes a Spemann’s organizer signal and binds and inhibits Bmp, Wnt and Nodal signalling. Cerberus 1 gain of function in early embryos induces ectopic head, heart and liver development, but head development remains normal in Cer1-deficient embryos. We report here that Cer1 exerts a positive effect on the control of ureteric bud branching, since Cer1 expression stimulates ureteric bud development, allowing more trifid and lateral branches develop rather than the bifid type during the early stages of organogenesis. Cer1 gain of function and knockout both change the 3D structure of the ureteric tree as revealed by optical projection tomography, and are associated with the inhibition of Bmp4 and the induction of Wnt11 and Gdnf expression. Cer1 binds Bmp2 and Bmp4 and serves as an inhibitor of Bmp4 signalling, and to some extent of canonical Wnt signalling. Genetic reduction of Wnt11 and excess Bmp4 in organ culture also reverse the Cer1stimulated processes to a considerable extent. Thus Cer1 takes part in MedChemExpress 169939-93-9 kidney development through fine tuning of the spatial organization of the ureteric bud-derived tree during kidney organogenesis by influencing Wnt, Gndf and Bmp signalling. transgene positive males were crossed with wild-type C57BL6 females to obtain embryos or mice for this purpose. The 
HoxB7/Cre and floxed Rosa26 yellow fluorescent protein mouse lines have been described previously, while the Cer1; Wnt11-/- and Cer1; HoxB7;Cre;YFPc/+ mouse lines were generated by crossing the Cer1;Wnt11+/- and HoxB7;Cre;YFPc/+ lines. The Cer1 knockout mouse has been described earlier. Dissection and culture of the embryonic kidney The kidneys were isolated at E11.5, incubated for one minute in 3% pancreatin/trypsin in Tyrode’s solution and the mesenchyme and ureteric bud separated out mechanically and subjected to RT-PCR. The kidneys were cultured in the presence of Gdnf or 100 ng/ml of Bmp4, fixed and processed for immunostaining according to Chi et al.. The culture times were as indicated in the Results section. RT- PCR The embryonic kidneys were dissected in ice-cold phosphatebuffered saline, pH 7.4, and total RN