April 30, 2012

One might think that once you’ve won your first Nobel Prize, it’s time to kick back and watch the youngsters do the dirty work of solving all of biology’s riddles. No so. Apparently, Nobel-ers don’t like to kick back at all, but continue to push the limits of our knowledge. I think they’re all wearing superhero capes underneath their biologist uniforms (plaid shirts and old jeans?). Today’s image is from the lab of Eric Wieschaus, in a paper that provides a fascinating alternative mechanism to the prevailing model of epithelial folding.

During development, groups of cells are shaped into tissues and organs in a process called morphogenesis. One of the earliest morphogenesis events is gastrulation, during which the embryo is organized into the three germ layers that will each develop into different tissues and organs. During gastrulation in the fruit fly, the dorsal side of the embryo undergoes two epithelial folds, the anterior and posterior dorsal transverse folds, at precise locations on the embryo. The current model of epithelial folding involves actin-myosin contractions that trigger the initial cell shape changes. Wang and colleagues recently found an alternative mechanism that underlies epithelial folding during fruit fly gastrulation. Specifically, Wang and colleagues found that the adherens junctions that form between epithelial cells relocate to more basal locations in the cells that initiate epithelial folding. The movement of adherens junctions, and in turn dorsal fold initiation, depends on the activity of the polarity proteins Bazooka and Par-1. In the images above, the initiation of anterior (pink arrow) and posterior (blue arrow) folds are visualized by high resolution live imaging. The localization of E-cadherin (white), a key adherens junction protein, drops from the apical surface (top of the cells) to a more basal location in the cells undergoing shape changes.

Wang, Y., Khan, Z., Kaschube, M., & Wieschaus, E. (2012). Differential positioning of adherens junctions is associated with initiation of epithelial folding Nature, 484 (7394), 390-393 DOI: 10.1038/nature10938

Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

April 26, 2012

One of my favorite analogies in cell biology revolves around cupcakes and asymmetric cell division, which happen to be two of the most wonderful things in the world. If you cut a cupcake in half down the center, you have two equal pieces with both icing and cake. Or, you can cut the cupcake in half across the center, and have one piece with just icing and one piece with just cake. Today’s image is from a paper describing how a cell divides to result into two equal icing-and-cake cells.

During development, the orientation of cell division within an epithelial sheet helps to drive tissue shape changes. Symmetric cell division, during which the mitotic spindle is parallel to the plane of the sheet, leads to tissue growth and elongation, while asymmetric division, during which the spindle is perpendicular to the epithelial sheet, causes tissue thickening and stratification. Most research on mitotic spindle orientation has focused on asymmetric cell division, but a recent paper describes interesting results on how a spindle is positioned during symmetric division. Woolner and Papalopulu looked at epithelial tissue in early frog embryos to test possible mechanisms of spindle positioning in symmetric cell divisions. As seen in the image above (left), the spindle is positioned precisely in the plane of the epithelial sheet. Woolner and Papalopulu found that a basally-directed force (pushing down, into the sheet) is provided by microtubules and myosin-10, while an apically-directed force is provided by actin filaments and myosin-2. Both of these forces are required to position the spindle in the plane of the epithelium, and at its proper position along the apical-basal axis. In the middle image above, the spindle is positioned near the apical cell surface after astral microtubules were disrupted. After actin-filament disruption (right image), spindles moved toward the basal cell surface.

Woolner, S., & Papalopulu, N. (2012). Spindle Position in Symmetric Cell Divisions during Epiboly Is Controlled by Opposing and Dynamic Apicobasal Forces Developmental Cell, 22 (4), 775-787 DOI: 10.1016/j.devcel.2012.01.002

Copyright ©2012 Elsevier Ltd. All rights reserved.

 

April 23, 2012

I love plants. I support our local botanical garden, I’ve been a vegetarian for almost 17 years, and I talk to (and hug) our yard’s new trees to welcome them to the family. Clearly I’m pro-plants. So why aren’t there more plant cell biology pictures on my blog? I have no excuses. Today, enjoy this lovely image from Arabidopsis, the go-to model plant in cell biology.

Rapid growth in a developing organism can provide challenges for the tissue, especially in tissues where the cells adhere to each other as they do in plants. In a developing plant, this rapid growth combined with differences in cell growth throughout the tissue causes mechanical strain and stress on the cells. A recent paper describes how katanin, a microtubule severing protein, is key in allowing the cells to respond to mechanical stress in the plant Arabidopsis. In this paper, Uyttewaal and colleagues imaged cell growth the in the plant’s stem cell niche, the shoot apical meristem, and found heterogeneity in the cell growth rates. Katanin mutants, however, had decreased growth variability in this same tissue. In normal plants, cortical microtubule arrays arrange themselves toward the regions of high mechanical stress, and this in turn affects growth. Uyttewaal and colleagues found that this directional arrangement of microtubule arrays is affected in katanin mutants, as seen in the images above. Images show shoot apical meristem tissue with microtubule arrays fluorescently tagged in green and their orientation marked in red. Microtubule arrays in wild type tissue (left) have a circumferential orientation in the peripheral zone (bottom, zoomed), while microtubule arrays in katanin mutants lacked a similar pattern (right images).

Uyttewaal, M., Burian, A., Alim, K., Landrein, B., Borowska-Wykręt, D., Dedieu, A., Peaucelle, A., Ludynia, M., Traas, J., Boudaoud, A., Kwiatkowska, D., & Hamant, O. (2012). Mechanical Stress Acts via Katanin to Amplify Differences in Growth Rate between Adjacent Cells in Arabidopsis Cell, 149 (2), 439-451 DOI: 10.1016/j.cell.2012.02.048
Copyright ©2012 Elsevier Ltd. All rights reserved.

April 19, 2012

“Location, Location, Location!” My husband and I have been watching too many house-hunting shows on HGTV (International Househunters FTW!), so the importance of location has been beaten into my brain. This real estate mantra applies in cell biology too. Today’s image is from a paper describing how the location of a dendrite can affect the strength of the synapse.

The synapse is the site of exchange between one neuron and another. The presynaptic terminal of a neuron’s axon will connect with, and send a signal to, the dendrite of another neuron. That dendrite is likely one of several that arise from the cell body of a neuron. A recent paper describes the relationship between the strength/function of the presynaptic terminal and the position of the dendrite, in certain neuron populations. According to de Jong and colleagues, the closer a dendrite is positioned to its own cell body, the higher the presynaptic strength of the axon connecting to it. In the images above, a cultured hippocampal neuron was stained for a marker of synaptic vesicles (left, green). The presynaptic strength was analyzed by the intensity of the synaptic vesicle staining and then color coded (middle), while the location of each synapse was measured as the distance from the cell body (right).

de Jong, A., Schmitz, S., Toonen, R., & Verhage, M. (2012). Dendritic position is a major determinant of presynaptic strength originally published in the Journal of Cell Biology, 197 (2), 327-337 DOI: 10.1083/jcb.201112135

April 16, 2012

I’m a homebody. I admit it. We’re all supposed to be adventurous, live on the edge, blah blah blah….but I thrive at home with my family around me. Maybe this makes me more like a stem cell than you glamorous jet-setters out there, and that seems pretty okay to me. Stem cells must stay in their niche, and a recent paper shows how some stem cells in the fruit fly do this through regulation of asymmetric division.

When adult stem cells divide, they produce a daughter cell that will take on a specific cell fate and another stem cell. To maintain this stem cell identity a stem cell must stay within its niche, or its microenvironment. In the fruit fly testes, germline stem cells (GSCs) stay adjacent to the “hub” within their niche and divide asymmetrically. In these divisions, a centrosome is positioned near the hub-GSC interface, and this aligns the mitotic spindle perpendicular to the hub. After cell division, the daughter cell that will remain a stem cell maintains its hub-GSC interface, while the differentiating cell is positioned further away. A recent paper shows that poor nutrient conditions prevent proper centrosome positioning in GSCs, which causes a delay in cell division via the centrosome orientation checkpoint. Roth and colleagues show that centrosome orientation is regulated by the insulin receptor pathway through its effect on the localization of Apc2, a cortical anchor for GSC centrosomes. The image above shows GSCs surrounding the hub (star) in a fruit fly testes cultured in poor nutrient conditions. One cell has correct centrosome orientation (yellow circle, centrosomes are red dots), while two cells (white circle) have misoriented centrosomes (arrowheads).

BONUS! Aren't GSCs pretty!? Check out these other posts on GSCs (here and here) that I wrote last week.

Roth, T., Chiang, C., Inaba, M., Yuan, H., Salzmann, V., Roth, C., & Yamashita, Y. (2012). Centrosome misorientation mediates slowing of the cell cycle under limited nutrient conditions in Drosophila male germline stem cells Molecular Biology of the Cell, 23 (8), 1524-1532 DOI: 10.1091/mbc.E11-12-0999

April 12, 2012

“Hang in there!” says the kitten dangling from a tree branch. Maybe this poster from my junior high-era bedroom should have had a white blood cell instead. While defending the body from infection, white blood cells have to anchor themselves to avoid being swept away from the constant blood flow around them. Today’s image is from a recent paper showing how this happens.

Leukocytes, or white blood cells, find their way to sites of infection in the body. Once there, leukocytes are subjected to the force of blood flow around them and must resist detachment from the inflamed tissue. Integrin cell adhesion proteins are important in stabilizing the anchors formed on leukocytes recruited to inflamed tissue. A recent paper shows that rapid actin polymerization at adhesion sites is triggered by the force of blood flow. In addition, Rullo and colleagues show that this actin polymerization is necessary for successful attachment. Image above shows human leukocytes on a surface coated with VCAM-1, a leukocyte adhesion molecule, and exposed to a fluid flow in the direction of the arrow. Arrowhead points to anchor points.

Rullo, J., Becker, H., Hyduk, S., Wong, J., Digby, G., Arora, P., Cano, A., Hartwig, J., McCulloch, C., & Cybulsky, M. (2012). Actin polymerization stabilizes 4 1 integrin anchors that mediate monocyte adhesion originally published in the Journal of Cell Biology, 197 (1), 115-129 DOI: 10.1083/jcb.201107140

April 9, 2012

Membranes really know how to mingle. They are dynamic in the cell—budding away from one organelle to fuse with another, remodeling themselves for the situation. My awkward party persona should take some notes…I’ve never seen membranes hang out next to the Chex Mix bowl all night. Today’s image is from a recent paper on membrane scission and the role of membrane remodeling proteins.

The membranes that compartmentalize a cell’s organelles are under constant transformation. Membrane sculpting is a coordinated process that includes bending membranes and remodeling by fission and fusion (severing and joining, respectively). Membrane curvature is introduced two different ways—by hydrophobic insertions into the membrane’s lipid bilayer, or by the presence of a scaffold made of curved BAR domain proteins. A recent paper sheds light on how these two membrane-remodeling mechanisms affects membrane fission. According to Boucrot and colleagues, the membrane insertion of a protein called epsin, which contains a hydrophobic ENTH domain, leads to membrane fission, while the curved BAR-domain scaffolds actually limit membrane fission. In addition, epsin is required for membrane fission of clathrin-coated vesicles. The electron micrograph above shows a clathrin-coated vesicle after depletion of all epsin proteins. Without epsin, vesicles are unable to bud from one another, creating a multi-headed structure.

Boucrot, E., Pick, A., Çamdere, G., Liska, N., Evergren, E., McMahon, H., & Kozlov, M. (2012). Membrane Fission Is Promoted by Insertion of Amphipathic Helices and Is Restricted by Crescent BAR Domains Cell, 149 (1), 124-136 DOI: 10.1016/j.cell.2012.01.047
Copyright ©2012 Elsevier Ltd. All rights reserved.

April 5, 2012

Sometimes I read something that elicits an old-school Joey Lawrence, “Whoa!” I may not be an early 90s heartthrob with voluminous hair, but sometimes the science world makes me sound like one. Today’s image is from a paper on emergence—not a particularly common topic in cell biology, but here the use of microtubules helps to model and test it.

Emergence describes the spontaneous order that can arise out of simple interactions of things. Examples of emergent phenomena in nature include flocks of birds, swarms of bees, ordered crystals of freezing water. The theories behind this collective behavior are tough to test due to the difficulty in controlling all variables and interactions. A recent paper, however, uses emergence at a cellular level to control for all interactions with only a few purified components. Here, Sumino and colleagues used purified microtubules propelled by dynein motors that were bound to a glass surface. Neighboring microtubules, which were on average 15um long, interacted by aligning with each other. Increased density of these local interactions resulted in the self-organization of microtubules into vortices about 400um in diameter, with microtubules rotating and sliding past each other in both clockwise and counter-clockwise directions. Image above shows a lattice formed from many vortices over time (three air bubbles are present with thicker edges).

BONUS! Check out movies from this paper here, under “Supplementary Information.” This one is my favorite!

Sumino, Y., Nagai, K., Shitaka, Y., Tanaka, D., Yoshikawa, K., Chaté, H., & Oiwa, K. (2012). Large-scale vortex lattice emerging from collectively moving microtubules Nature, 483 (7390), 448-452 DOI: 10.1038/nature10874
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

April 2, 2012

A good chunk of my personal pride is about my ability to wear several hats. I can cook a mean dinner, read that awesome new Myo10 paper, and fix a leaking faucet all while braiding my little girl’s hair and constructing a garden scene out of PlayDoh. So, today’s image makes me tip my many hats to Myo10 and its newly-recognized role in polarized cells.

Myo10 is a member of the giant family of myosin actin motors. Myo10 localizes to the tips of thin actin-rich membrane extensions, called filopodia, in non-polarized fibroblast-like cells and plays an important role in the formation and function of filopodia. A recent paper describes the role of Myo10 in a very different type of cell—the polarized epithelial cell. According to Liu and colleagues, Myo10 is important during formation of the cell-cell junctions that adhere epithelial cells together in a highly organized sheet. Myo10 is found at cell-cell contact points during junction formation, and helps ensure the timely localization of essential junction proteins. In addition, the leak-proof barrier function of an epithelial sheet is compromised in cells with reduced levels of Myo10. The images above show epithelial cysts, frequently used to model the three-dimensional formation of epithelial tissue in culture. Cysts with normal levels of Myo10 (top row) developed a single lumen, while cysts with reduced levels of Myo10 frequently had more than one lumen (bottom row), pointing to a role for Myo10 in epithelial morphogenesis. Junctional markers (ZO-1 is green, E-cadherin is red), however, are still properly localized in cysts with reduced Myo10.

Liu, K., Jacobs, D., Dunn, B., Fanning, A., & Cheney, R. (2012). Myosin-X Functions in Polarized Epithelial Cells Molecular Biology of the Cell DOI: 10.1091/mbc.E11-04-0358