During kidney branching, progenitor cells expressing the Ret receptor tyrosine kinase are found at the tips of ureteric buds (UBs), but downregulate Ret expression when they leave the UB tip to form ducts. Previous work has shown that Ret ablation excludes cells from UB tips. Now, Frank Costantini and colleagues investigate the reverse question: does maintained expression of Ret affect UB cell behaviour? First, the authors construct mice lines in which wild-type (Rosa26RetWT) or constitutively active (RosaRetPTC2) Ret can be permanently activated in individual UB cells. Using a kidney explant system, they show that both Rosa26RetWT and RosaRetPTC clones are ‘trapped’ in UB tips for several branching cycles. In mesenchyme-free UB organoids, forced expression of Ret causes cells to cluster and form new buds at random locations in the UB epithelium. This suggests that, in the intact kidney, the mesenchyme provides cues to guide Ret-expressing cells. Finally, the authors show through time-lapse imaging that clusters are formed by dynamic convergent cell movements or because cells fail to disperse during proliferation. Together, these data provide new insights into the role of Ret in regulating UB cells during kidney branching.
Ret makes ureteric bud tip-seeking cells
Ret makes ureteric bud tip-seeking cells. Development 1 May 2021; 148 (9): e148_e0902. doi:
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