Browsing by Subject "cell migration"

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  • Mogollon, Isabel; Ahtiainen, Laura (2020)
    Embryonic development of ectodermal organs involves a very dynamic range of cellular events and, therefore, requires advanced techniques to visualize them. Ectodermal organogenesis proceeds in well-defined sequential stages mediated by tissue interactions. Different ectodermal organs feature shared morphological characteristics, which are regulated by conserved and reiterative signaling pathways. A wealth of genetic information on the expression patterns and interactions of specific signaling pathways has accumulated over the years. However, the conventional developmental biology methods have mainly relied on two-dimensional tissue histological analyses at fixed time points limiting the possibilities to follow the processes in real time on a single cell resolution. This has complicated the interpretation of cause and effect relationships and mechanisms of the successive events. Whole-mount tissue live imaging approaches are now revealing how reshaping of the epithelial sheet for the initial placodal thickening, budding morphogenesis and beyond, involve coordinated four dimensional changes in cell shapes, well-orchestrated cell movements and specific cell proliferation and apoptosis patterns. It is becoming evident that the interpretation of the reiterative morphogenic signals takes place dynamically at the cellular level. Depending on the context, location, and timing they drive different cell fate choices and cellular interactions regulating a pattern of behaviors that ultimately defines organ shapes and sizes. Here we review how new tissue models, advances in 3D and live tissue imaging techniques have brought new understanding on the cell level behaviors that contribute to the highly dynamic stages of morphogenesis in teeth, hair and related ectodermal organs during development, and in dysplasia contexts.
  • Jiu, Yaming; Kumari, Reena; Fenix, Aidan M.; Schaible, Niccole; Liu, Xiaonan; Varjosalo, Markku; Krishnan, Ramaswamy; Burnette, Dylan T.; Lappalainen, Pekka (2019)
    Summary Cell adhesion, morphogenesis, mechanosensing, and muscle contraction rely on contractile actomyosin bundles, where the force is produced through sliding of bipolar myosin II filaments along actin filaments. The assembly of contractile actomyosin bundles involves registered alignment of myosin II filaments and their subsequent fusion into large stacks. However, mechanisms underlying the assembly of myosin II stacks and their physiological functions have remained elusive. Here, we identified myosin-18B, an unconventional myosin, as a stable component of contractile stress fibers. Myosin-18B co-localized with myosin II motor domains in stress fibers and was enriched at the ends of myosin II stacks. Importantly, myosin-18B deletion resulted in drastic defects in the concatenation and persistent association of myosin II filaments with each other and thus led to severely impaired assembly of myosin II stacks. Consequently, lack of myosin-18B resulted in defective maturation of actomyosin bundles from their precursors in osteosarcoma cells. Moreover, myosin-18B knockout cells displayed abnormal morphogenesis, migration, and ability to exert forces to the environment. These results reveal a critical role for myosin-18B in myosin II stack assembly and provide evidence that myosin II stacks are important for a variety of vital processes in cells.
  • Kovac, Bianca (Helsingfors universitet, 2010)
    Actin stress fibers are dynamic structures in the cytoskeleton, which respond to mechanical stimuli and affect cell motility, adhesion and invasion of cancer cells. In nonmuscle cells, stress fibers have been subcategorized to three distinct stress fiber types: dorsal and ventral stress fibers and transverse arcs. These stress fibers are dissimilar in their subcellular localization, connection to substratum as well as in their dynamics and assembly mechanisms. Still uncharacterized is how they differ in their function and molecular composition. Here, I have studied involvement of nonmuscle alpha-actinin-1 and -4 in regulating distinct stress fibers as well as their localization and function in human U2OS osteosarcoma cells. Except for the correlation of upregulation of alpha-actinin-4 in invasive cancer types very little is known about whether these two actinins are redundant or have specific roles. The availability of highly specific alpha-actinin-1 antibody generated in the lab, revealed localization of alpha-actinin-1 along all three categories of stress fibers while alphaactinin-4 was detected at cell edge, distal ends of stress fibers as well as perinuclear regions. Strikingly, by utilizing RNAi-mediated gene silencing of alpha-actinin-1 resulted in specific loss of dorsal stress fibers and relocalization of alpha-actinin-4 to remaining transverse arcs and ventral stress fibers. Unexpectedly, aberrant migration was not detected in cells lacking alpha-actinin-1 even though focal adhesions were significantly smaller and fewer. Whereas, silencing of alpha-actinin-4 noticeably affected overall cell migration. In summary, as part of my master thesis study I have been able to demonstrate distinct localization and functional patterns for both alpha-actinin-1 and -4. I have identified alpha-actinin-1 to be a selective dorsal stress fiber crosslinking protein as well as to be required for focal adhesion maturation, while alpha-actinin-4 was demonstrated to be fundamental for cell migration.