| First Author | Keefe Davis T | Year | 2013 |
| Journal | Mech Dev | Volume | 130 |
| Issue | 9-10 | Pages | 506-18 |
| PubMed ID | 23542432 | Mgi Jnum | J:199323 |
| Mgi Id | MGI:5502273 | Doi | 10.1016/j.mod.2013.03.001 |
| Citation | Keefe Davis T, et al. (2013) Stage specific requirement of Gfralpha1 in the ureteric epithelium during kidney development. Mech Dev 130(9-10):506-18 |
| abstractText | Glial cell line-derived neurotrophic factor (GDNF) binds a coreceptor GDNF family receptor alpha1 (GFRalpha1) and forms a signaling complex with the receptor tyrosine kinase RET. GDNF-GFRalpha1-RET signaling activates cellular pathways that are required for normal induction of the ureteric bud (UB) from the Wolffian duct (WD). Failure of UB formation results in bilateral renal agenesis and perinatal lethality. Gfralpha1 is expressed in both the epithelial and mesenchymal compartments of the developing kidney while Ret expression is specific to the epithelium. The biological importance of Gfralpha1's wider tissue expression and its role in later kidney development are unclear. We discovered that conditional loss of Gfralpha1 in the WD epithelium prior to UB branching is sufficient to cause renal agenesis. This finding indicates that Gfralpha1 expressed in the nonepithelial structures cannot compensate for this loss. To determine Gfralpha1's role in branching morphogenesis after UB induction we used an inducible Gfralpha1-specific Cre-deletor strain and deleted Gfralpha1 from the majority of UB tip cells post UB induction in vivo and in explant kidney cultures. We report that Gfralpha1 excision from the epithelia compartment after UB induction caused a modest reduction in branching morphogenesis. The loss of Gfralpha1 from UB-tip cells resulted in reduced cell proliferation and decreased activated ERK (pERK). Further, cells without Gfralpha1 expression are able to populate the branching UB tips. These findings delineate previously unclear biological roles of Gfralpha1 in the urinary tract and demonstrate its cell-type and stage-specific requirements in kidney development. |
