Regulation of Cytoskeletal Dynamics

我的研究方向是细胞分裂的胞内控制，在有丝分裂过程中将母细胞分离成子细胞，以及组织形态发生过程中细胞集体运动的胞间控制。这些研究主题与我们对细胞骨架动力学调节的兴趣有关，尤其是肌动球蛋白细丝。对于细胞质分裂，我们研究了精确控制肌动球蛋白环夹紧细胞质和细胞膜的机制。这个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被恰当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，并且推导了几个模型来解释这在不同细胞类型和生物体中如何起作用。然而，这些研究大多是在模式生物的单细胞上进行的，或者使用培养皿中生长的癌细胞。我们发现了另一条通过染色质与有丝分裂纺锤体平行调节细胞分裂的途径。这个途径可以帮助我们理解细胞分裂是如何在不同的细胞中被独特地调节的，我们将在对发育重要的细胞中研究这个途径；极性不同，倍性改变或大小不同。

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.