Schambony Alexandra, Wedlich Doris
Universitaet Karlsruhe (TH), Zoologisches Institut II, Kaiserstrasse 12, D-76128 Karlsruhe, Germany.
Dev Cell. 2007 May;12(5):779-92. doi: 10.1016/j.devcel.2007.02.016.
XWnt-5A, a member of the nontransforming Wnt-5A class of Wnt ligands, is required for convergent extension movements in Xenopus embryos. XWnt-5A knockdown phenocopies paraxial protocadherin (XPAPC) loss of function: involuted mesodermal cells fail to align mediolaterally, which results in aberrant movements and a selective inhibition of constriction. XWnt-5A depletion was rescued by coinjection of XPAPC RNA, indicating that XWnt-5A acts upstream of XPAPC. XWnt-5A, but not XWnt-11, stimulates XPAPC expression independent of the canonical Wnt/beta-catenin pathway. We show that transcriptional regulation of XPAPC by XWnt-5A requires the receptor tyrosine kinase Ror2. XWnt-5A/Xror2 signal through PI3 kinase and cdc42 to activate the JNK signaling cascade with the transcription factors ATF2 and c-jun. The Wnt-5A/Ror2 pathway represents an alternative, distinct branch of noncanonical Wnt signaling that controls gene expression and is required in the regulation of convergent extension movements in Xenopus gastrulation.
XWnt-5A是Wnt配体中不具有转化能力的Wnt-5A类成员之一，非洲爪蟾胚胎的汇聚延伸运动需要它。XWnt-5A基因敲低模拟了近轴原钙黏蛋白（XPAPC）功能丧失的表型：内卷的中胚层细胞无法在中侧对齐，这导致异常运动并选择性抑制收缩。通过共注射XPAPC RNA可挽救XWnt-5A的缺失，表明XWnt-5A在XPAPC上游起作用。XWnt-5A而非XWnt-11可独立于经典Wnt/β-连环蛋白途径刺激XPAPC表达。我们发现XWnt-5A对XPAPC的转录调控需要受体酪氨酸激酶Ror2。XWnt-5A/Ror2通过PI3激酶和cdc42信号激活JNK信号级联反应以及转录因子ATF2和c-jun。Wnt-5A/Ror2途径代表了非经典Wnt信号传导的另一个独特分支，它控制基因表达，并且在非洲爪蟾原肠胚形成过程中对汇聚延伸运动的调节是必需的。
