Regulation of Cytoskeletal Dynamics

细胞骨架动力学的调节

• 批准号: RGPIN-2016-04012
• 负责人: Piekny, Alisa
• 金额: $ 2.4万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614780
• 关键词: Regulation; Cytoskeletal; Dynamics

My research program studies the intracellular control of cytokinesis, which separates mother cells into daughters during mitosis, and intercellular control of collective cell movements for tissue morphogenesis. These research themes are tied by our interest in the regulation of cytoskeletal dynamics, and actomyosin filaments in particular. For cytokinesis, we study mechanisms that precisely control the actomyosin ring that pinches in the cytosol and membrane of cells. The ring must be spatiotemporally controlled to ensure that the chromosomes and cell fate determinants are properly inherited into each daughter cell. Prior studies showed that the mitotic spindle provides cues to regulate actomyosin ring formation, and several models were derived to explain how this could work in different cell types and organisms. However, the majority of these studies were done on single cells in model organisms, or using cancer cells grown in a dish. We uncovered another pathway that functions via chromatin to regulate cytokinesis in parallel with the mitotic spindle. This pathway may help us to understand how cytokinesis is uniquely regulated in different cells, and we will study this pathway in cells that are important for development; with different polarity, altered ploidy or different size. For tissue morphogenesis, we study mechanisms that coordinate actomyosin regulation of cell shape changes and migration. The failure to coordinate cells can prevent tissues from developing properly. However, few studies have followed tissue morphogenesis in vivo, and it is not clear how intercellular signaling coordinates cells within or between tissues. Further, most studies of morphogenesis were done using isolated epidermal tissue, and the development of other tissues is less-well understood. We use C. elegans as a model organism due to their simple body plan, amenability to microscopy and their establishment as a genetic model. We found that during C. elegans epidermal morphogenesis, a subset of neuroblasts (neuronal precursor cells) undergo morphogenesis concomitant with the overlying epidermis. The neuroblasts shrink in surface area and undergo organizational changes, and we found that altering myosin contractility selectively in these cells disrupts migration of the overlying epidermal cells. Therefore, we are well-positioned to further characterize neuroblast morphogenesis, a non-epidermal tissue that is crucial for metazoans. Also, we will determine how mechanical forces coordinate neuroblast and epidermal morphogenesis.

我的研究项目研究胞质分裂的细胞内控制，在有丝分裂过程中将母细胞分离成子细胞，以及组织形态发生的集体细胞运动的细胞间控制。这些研究主题与我们对细胞骨架动力学调节的兴趣有关，特别是肌动球蛋白丝。对于胞质分裂，我们研究了精确控制肌动球蛋白环的机制，肌动球蛋白环在细胞质和细胞膜中收缩。环必须在时空上受到控制，以确保染色体和细胞命运决定因素正确地遗传到每个子细胞中。先前的研究表明，有丝分裂纺锤体提供了调节肌动球蛋白环形成的线索，并且衍生了几种模型来解释这如何在不同的细胞类型和生物体中起作用。然而，这些研究中的大多数都是在模型生物体中的单细胞上进行的，或者使用在培养皿中生长的癌细胞。我们发现了另一个途径，通过染色质的功能，以调节胞质分裂平行有丝分裂纺锤体。这种途径可能有助于我们了解胞质分裂在不同细胞中是如何独特调节的，我们将在对发育重要的细胞中研究这种途径;具有不同极性，改变倍性或不同大小。 对于组织形态发生，我们研究了协调肌动球蛋白调节细胞形状变化和迁移的机制。协调细胞的失败会阻止组织正常发育。然而，很少有研究在体内跟踪组织形态发生，并且尚不清楚细胞间信号传导如何协调组织内或组织间的细胞。此外，大多数形态发生的研究都是使用分离的表皮组织进行的，而其他组织的发育则不太清楚。我们使用C。由于其简单的体型、对显微镜的适应性以及作为遗传模型的建立，线虫被认为是模式生物。我们发现，在C。秀丽线虫表皮形态发生，神经母细胞（神经元前体细胞）的一个子集伴随着上覆表皮经历形态发生。神经母细胞的表面积缩小，并发生组织变化，我们发现，选择性地改变这些细胞中的肌球蛋白收缩性会破坏覆盖表皮细胞的迁移。因此，我们处于有利地位，以进一步表征成神经细胞形态发生，非表皮组织，是至关重要的后生动物。此外，我们将确定机械力如何协调成神经细胞和表皮形态发生。