University of Zürich, Institute of Molecular Life Sciences, Winterthurerstrasse 190, CH-8057, Switzerland.
Dev Cell. 2012 Sep 11;23(3):494-506. doi: 10.1016/j.devcel.2012.06.019.
Morphogenesis is a developmental phase during which cell fates are executed. Mechanical forces shaping individual cells play a key role during tissue morphogenesis. By investigating morphogenesis of the Caenorhabditis elegans hermaphrodite vulva, we show that the force-generating actomyosin network is differentially regulated by NOTCH and EGFR/RAS/MAPK signaling to shape the vulval tube. NOTCH signaling activates expression of the RHO kinase LET-502 in the secondary cell lineage through the ETS-family transcription factor LIN-1. LET-502 induces actomyosin-mediated contraction of the apical lumen in the secondary toroids, thereby generating a dorsal pushing force. In contrast, MAPK signaling in the primary lineage downregulates LET-502 RHO kinase expression to prevent toroid contraction and allow the gonadal anchor cell to expand the dorsal lumen of the primary toroids. The antagonistic action of the MAPK and NOTCH pathways thus controls vulval tube morphogenesis linking cell fate specification to morphogenesis.
形态发生是一个细胞命运执行的发育阶段。塑造单个细胞的机械力在组织形态发生中起着关键作用。通过研究秀丽隐杆线虫雌雄同体的阴门形态发生，我们表明，肌动球蛋白网络的产生力受到 NOTCH 和 EGFR/RAS/MAPK 信号的差异调节，以塑造阴门管。NOTCH 信号通过 ETS 家族转录因子 LIN-1在次级细胞谱系中激活 RHO 激酶 LET-502 的表达。LET-502 诱导次级环中的顶端腔中的肌动球蛋白介导的收缩，从而产生背向推力。相比之下，初级谱系中的 MAPK 信号下调 LET-502 RHO 激酶的表达，以防止环的收缩，并允许性腺锚细胞扩展初级环的背向腔。因此，MAPK 和 NOTCH 途径的拮抗作用控制着阴门管形态发生，将细胞命运特化与形态发生联系起来。
