| First Author | Tee JB | Year | 2013 |
| Journal | Biol Open | Volume | 2 |
| Issue | 9 | Pages | 952-9 |
| PubMed ID | 24143282 | Mgi Jnum | J:201043 |
| Mgi Id | MGI:5510780 | Doi | 10.1242/bio.20135595 |
| Citation | Tee JB, et al. (2013) GDNF-independent ureteric budding: role of PI3K-independent activation of AKT and FOSB/JUN/AP-1 signaling. Biol Open 2(9):952-9 |
| abstractText | A significant fraction of mice deficient in either glial cell-derived neurotrophic factor (GDNF) or its co-receptors (Gfralpha1, Ret), undergoes ureteric bud (UB) outgrowth leading to the formation of a rudimentary kidney. Previous studies using the isolated Wolffian duct (WD) culture indicate that activation of fibroblast growth factor (FGF) receptor signaling, together with suppression of BMP/Activin signaling, is critical for GDNF-independent WD budding (Maeshima et al., 2007). By expression analysis of embryonic kidney from Ret((-/-)) mice, we found the upregulation of several FGFs, including FGF7. To examine the intracellular pathways, we then analyzed GDNF-dependent and GDNF-independent budding in the isolated WD culture. In both conditions, Akt activation was found to be important; however, whereas this occurred through PI3-kinase in GDNF-dependent budding, in the case of GDNF-independent budding, Akt activation was apparently via a PI3-kinase independent mechanism. Jnk signaling and the AP-1 transcription factor complex were also implicated in GDNF-independent budding. FosB, a binding partner of c-Jun in the formation of AP-1, was the most highly upregulated gene in the ret knockout kidney (in which budding had still occurred), and we found that its siRNA-mediated knockdown in isolated WDs also blocked GDNF-independent budding. Taken together with the finding that inhibition of Jnk signaling does not block Akt activation/phosphorylation in GDNF-independent budding, the data support necessary roles for both FosB/Jun/AP-1 signaling and PI3-kinase-independent activation of Akt in GDNF-independent budding. A model is proposed for signaling events that involve Akt and JNK working to regulate GDNF-independent WD budding. |
