Huang Shuyi, Shetty Premnath, Robertson Scott M, Lin Rueyling
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Development. 2007 Jul;134(14):2685-95. doi: 10.1242/dev.008268. Epub 2007 Jun 13.
C. elegans embryos exhibit an invariant lineage comprised primarily of a stepwise binary diversification of anterior-posterior (A-P) blastomere identities. This binary cell fate specification requires input from both the Wnt and MAP kinase signaling pathways. The nuclear level of the TCF protein POP-1 is lowered in all posterior cells. We show here that the beta-catenin SYS-1 also exhibits reiterated asymmetry throughout multiple A-P divisions and that this asymmetry is reciprocal to that of POP-1. Furthermore, we show that SYS-1 functions as a coactivator for POP-1, and that the SYS-1-to-POP-1 ratio appears critical for both the anterior and posterior cell fates. A high ratio drives posterior cell fates, whereas a low ratio drives anterior cell fates. We show that the SYS-1 and POP-1 asymmetries are regulated independently, each by a subset of genes in the Wnt/MAP kinase pathways. We propose that two genetic pathways, one increasing SYS-1 and the other decreasing POP-1 levels, robustly elevate the SYS-1-to-POP-1 ratio in the posterior cell, thereby driving A-P differential cell fates.
秀丽隐杆线虫胚胎表现出一种固定不变的细胞谱系，主要由前后（A-P）裂球身份的逐步二元分化组成。这种二元细胞命运的决定需要Wnt和丝裂原活化蛋白激酶（MAP激酶）信号通路的输入。TCF蛋白POP-1在所有后体细胞中的核水平降低。我们在此表明，β-连环蛋白SYS-1在多个A-P分裂过程中也表现出反复的不对称性，并且这种不对称性与POP-1的不对称性相反。此外，我们表明SYS-1作为POP-1的共激活因子发挥作用，并且SYS-1与POP-1的比例对于前后细胞命运似乎都至关重要。高比例驱动后体细胞命运，而低比例驱动前体细胞命运。我们表明SYS-1和POP-1的不对称性是独立调节的，各自由Wnt/MAP激酶信号通路中的一组基因调节。我们提出，两条遗传途径，一条增加SYS-1水平，另一条降低POP-1水平，有力地提高了后体细胞中SYS-1与POP-1的比例，从而驱动A-P细胞命运差异。
