English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

GDNF signaling through the Ret receptor tyrosine kinase (RTK) is required for ureteric bud (UB) branching morphogenesis during kidney development in mice and humans. Furthermore, many other mutant genes that cause renal agenesis exert their effects via the GDNF/RET pathway. Therefore, RET signaling is believed to play a central role in renal organogenesis. Here, we re-examine the extent to which the functions of  Gdnf  and  Ret  are unique, by seeking conditions in which a kidney can develop in their absence. We find that in the absence of the negative regulator  Spry1 ,  Gdnf , and  Ret  are no longer required for extensive kidney development.  Gdnf−/−;Spry1−/−  or  Ret−/−;Spry1−/−  double mutants develop large kidneys with normal ureters, highly branched collecting ducts, extensive nephrogenesis, and normal histoarchitecture. However, despite extensive branching, the UB displays alterations in branch spacing, angle, and frequency. UB branching in the absence of  Gdnf  and  Spry1  requires  Fgf10  (which normally plays a minor role), as removal of even one copy of  Fgf10  in  Gdnf−/−;Spry1−/−  mutants causes a complete failure of ureter and kidney development. In contrast to  Gdnf  or  Ret  mutations, renal agenesis caused by concomitant lack of the transcription factors ETV4 and ETV5 is not rescued by removing  Spry1 , consistent with their role downstream of both RET and FGFRs. This shows that, for many aspects of renal development, the balance between positive signaling by RTKs and negative regulation of this signaling by SPRY1 is more critical than the specific role of GDNF. Other signals, including FGF10, can perform many of the functions of GDNF, when SPRY1 is absent. But GDNF/RET signaling has an apparently unique function in determining normal branching pattern. In contrast to GDNF or FGF10,  Etv4  and  Etv5  represent a critical node in the RTK signaling network that cannot by bypassed by reducing the negative regulation of upstream signals.

Kidney Development in the Absence of Gdnf and Spry1 Requires Fgf10