Department of Developmental Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Development. 2011 Oct;138(20):4375-85. doi: 10.1242/dev.066431.
Tissue-specific stem cells combine proliferative and asymmetric divisions to balance self-renewal with differentiation. Tight regulation of the orientation and plane of cell division is crucial in this process. Here, we study the reproducible pattern of anterior-posterior-oriented stem cell-like divisions in the Caenorhabditis elegans seam epithelium. In a genetic screen, we identified an alg-1 Argonaute mutant with additional and abnormally oriented seam cell divisions. ALG-1 is the main subunit of the microRNA-induced silencing complex (miRISC) and was previously shown to regulate the timing of postembryonic development. Time-lapse fluorescence microscopy of developing larvae revealed that reduced alg-1 function successively interferes with Wnt signaling, cell adhesion, cell shape and the orientation and timing of seam cell division. We found that Wnt inactivation, through mig-14 Wntless mutation, disrupts tissue polarity but not anterior-posterior division. However, combined Wnt inhibition and cell shape alteration resulted in disordered orientation of seam cell division, similar to the alg-1 mutant. Our findings reveal additional alg-1-regulated processes, uncover a previously unknown function of Wnt ligands in seam tissue polarity, and show that Wnt signaling and geometric cues redundantly control the seam cell division axis.
组织特异性干细胞通过增殖和不对称分裂来平衡自我更新和分化。在这个过程中，细胞分裂的方向和平面的严格调节至关重要。在这里，我们研究了秀丽隐杆线虫体壁上皮中前后定向干细胞样分裂的可重复模式。在遗传筛选中，我们鉴定出一个 alg-1 Argonaute 突变体，具有额外的和异常定向的体壁细胞分裂。ALG-1 是 microRNA 诱导的沉默复合物（miRISC）的主要亚基，先前被证明调节胚胎后发育的时间。发育幼虫的延时荧光显微镜观察显示，alg-1 功能降低依次干扰 Wnt 信号、细胞黏附、细胞形状以及体壁细胞分裂的方向和时间。我们发现，通过 mig-14 Wntless 突变失活 Wnt，破坏了组织极性，但不破坏前后分裂。然而，联合 Wnt 抑制和细胞形状改变导致体壁细胞分裂方向紊乱，类似于 alg-1 突变体。我们的研究结果揭示了额外的 alg-1 调节过程，揭示了 Wnt 配体在体壁组织极性中的一个先前未知的功能，并表明 Wnt 信号和几何线索冗余地控制体壁细胞分裂轴。
