Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension.
Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension.
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非经典 Wnt5a/Ror2 信号通过控制中间中胚层延伸来调节肾脏形态发生。
DOI：
10.1093/hmg/ddu397
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发表时间：
2014
影响因子：
3.5
通讯作者：
Perantoni,AlanO
中科院分区：
文献类型：
--
作者：
Yun,Kangsun;Ajima,Rieko;Sharma,Nirmala;Costantini,Frank;Mackem,Susan;Lewandoski,Mark;Yamaguchi,TerryP;Perantoni,AlanO
Congenital anomalies of the kidney and urinary tract (CAKUT) affect about 1 in 500 births and are a major cause of morbidity in infants. Duplex collecting systems rank among the most common abnormalities of CAKUT, but the molecular basis for this defect is poorly understood. In mice, conditional deletion ofWnt5ain mesoderm results in bilateral duplex kidney and ureter formation. The ureteric buds (UBs) in mutants emerge as doublets from the intermediate mesoderm (IM)-derived nephric duct (ND) without anterior expansion of the glial cell line-derived neurotrophic factor (Gdnf) expression domain in the surrounding mesenchyme.Wnt5ais normally expressed in a graded manner at the posterior end of the IM, but its expression is down-regulated prior to UB outgrowth at E10.5. Furthermore, ablation of Wnt5a in the mesoderm with an inducible Cre at E7.5 results in duplex UBs, whereas ablation at E8.5 yields normal UB outgrowth, demonstrating that Wnt5a functions in IM development well before the formation of the metanephros. In mutants, the posterior ND is duplicated and surrounding Pax2-positive mesenchymal cells persist in the nephric cord, suggesting that disruption of normal ND patterning prompts the formation of duplex ureters and kidneys.Ror2homozygous mutants, which infrequently yield duplex collecting systems, show a dramatic increase in incidence with the additional deletion of one copy of Wnt5a, implicating this receptor in non-canonical Wnt5a signaling during IM development. This work provides the first evidence of a role of Wnt5a/Ror2 signaling in IM extension and offers new insights into the etiology of CAKUT and possible involvement of Wnt5a/Ror2 mutations.
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影响因子：
11.8
作者：
Gray, Ryan S.;Roszko, Isabelle;Solnica-Krezel, Lilianna
通讯作者：
Solnica-Krezel, Lilianna
影响因子：
11.8
作者：
Costantini, Frank;Kopan, Raphael
通讯作者：
Kopan, Raphael
影响因子：
11.8
作者：
Grieshammer, U;Ma, L;Martin, GR
通讯作者：
Martin, GR
散乱介导的平面细胞极性信号传导是第二心田谱系中流出道形态发生所必需的。
影响因子：
2.7
作者：
Sinha T;Wang B;Evans S;Wynshaw-Boris A;Wang J
通讯作者：
Wang J
影响因子：
4.8
作者：
Wang H;Yang Y;Sharma N;Tarasova NI;Timofeeva OA;Winkler-Pickett RT;Tanigawa S;Perantoni AO
通讯作者：
Perantoni AO