Qi Xiaoyuan, Okinaka Yuka, Nishita Michiru, Minami Yasuhiro
Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
Genes Cells. 2016 Apr;21(4):325-34. doi: 10.1111/gtc.12342. Epub 2016 Feb 3.
Spatiotemporally regulated interaction between the metanephric mesenchyme (MM) and Wolffian duct (WD) is essential for the induction of a single ureteric bud (UB). The MM then interacts with the tip of the UB to induce outgrowth and branching of the UB, which in turn promotes growth of the adjacent MM. The Ror family receptor tyrosine kinases, Ror1 and Ror2, have been shown to act as receptors for Wnt5a to mediate noncanonical Wnt signaling. Previous studies have shown that Ror2-mutant mice exhibit ectopic formation of the UB, due to abnormal juxtaposition of the MM to the WD. We show here that both Ror1 and Ror2 are expressed in the mesenchyme between the MM and WD during UB formation. Although Ror1-mutant mice show no apparent defects in UB formation, Ror1;Ror2-double-mutant mice exhibit either defects in UB outgrowth and branching morphogenesis, associated with the loss of the MM from the UB domain, or ectopic formation of the UB. We also show genetic interactions between Ror1 and Wnt5a during UB formation. These findings suggest that Wnt5a-Ror1/Ror2 signaling regulates cooperatively the formation of the MM at the proper position to ensure normal development of the UB.
后肾间充质（MM）与中肾管（WD）之间的时空调节相互作用对于诱导单个输尿管芽（UB）至关重要。然后，MM与UB的尖端相互作用，诱导UB的生长和分支，这反过来又促进相邻MM的生长。Ror家族受体酪氨酸激酶Ror1和Ror2已被证明作为Wnt5a的受体来介导非经典Wnt信号传导。先前的研究表明，由于MM与WD的异常并置，Ror2突变小鼠表现出UB的异位形成。我们在此表明，在UB形成过程中，Ror1和Ror2均在MM与WD之间的间充质中表达。虽然Ror1突变小鼠在UB形成中未表现出明显缺陷，但Ror1;Ror2双突变小鼠表现出UB生长和分支形态发生的缺陷，与MM从UB区域丢失相关，或UB的异位形成。我们还展示了在UB形成过程中Ror1与Wnt5a之间的遗传相互作用。这些发现表明，Wnt5a-Ror1/Ror2信号传导协同调节MM在适当位置的形成，以确保UB的正常发育。
