April 10, 2014

When you host a party at your home, do you hire a caterer to bring in food or do you cook the food right there in your kitchen? One of these options leaves a lot more wiggle room for last-minute changes—a few extra guests, a gluten allergy, a pregnant lady with a disgust for wobbly desserts. A cell recognizes this distinction too. When making certain proteins, a cell will synthesize proteins where and when they’re needed. Today’s image is from Natasha Gutierrez, who recently published a study describing the role of β-actin mRNA and monomer synthesis in adherens junction assembly.

The actin cytoskeleton is made of actin filaments and countless actin-regulating proteins that guide the ever-changing dynamics of the cytoskeleton. Actin filament polymerization is regulated by localized synthesis of β-actin monomers from β-actin mRNA. A recent paper by Gutierrez and colleagues shows that the assembly of adherens junctions (AJs), epithelial cell-cell adhesion structures, requires localized β-actin monomer synthesis, the β-actin 3’ UTR and β-actin mRNA zipcode sequence at cell-cell contact sites. Additionally, active RhoA, which targets zipcode-mediated β-actin mRNA localization, is localized to cell-cell contact sites. In the unpublished images above, mammalian cells were treated with increasing levels (top to bottom) of a Rho inhibitor. The ability to form AJs, seen as the colocalization of actin filaments (left, green in merged) and E-cadherin (middle, red in merged) at cell-cell contact sites, decreased with increasing levels of the Rho inhibitor.

Gutierrez, N., Eromobor, I., Petrie, R., Vedula, P., Cruz, L., & Rodriguez, A. (2014). The B-actin mRNA zipcode regulates epithelial adherens junction assembly but not maintenance RNA DOI: 10.1261/rna.043208.113

May 13, 2013

Molecular motors are some of the raddest things in a cell.  They can walk along cytoskeletal elements such as microtubules and actin filaments, and the list of cellular events that they participate in is a long, long list.  Today’s image is from a paper showing a beautiful pattern of nonmuscle myosin II in epithelial cells.

Epithelial cells assemble junctions to adhere to one another, and the actin motor nonmuscle myosin II (NMII) is a major component of these epithelial apical junctions.  NMII helps the epithelial sheet respond to morphogenesis and changes in tissue homeostasis, and a recent paper describes how the network of NMII motors does so.  Ebrahim and colleagues have found that NMII in the apical junctional complex of epithelial cells assembles into precise muscle-like sarcomere units that form a belt around each cell.  The sarcomeres of neighboring cells are aligned, in turn assembling into a contractile network that can result in changes in cell shape.  In the images above, NMII (green) is seen in repeated sarcomere units around each cell (actin is in red).  NMII puncta are paired together in neighboring cells.  Arrows (middle) point to the junctions between three cells, seen at higher magnification on the right.

Ebrahim, S., Fujita, T., Millis, B., Kozin, E., Ma, X., Kawamoto, S., Baird, M., Davidson, M., Yonemura, S., Hisa, Y., Conti, M., Adelstein, R., Sakaguchi, H., & Kachar, B. (2013). NMII Forms a Contractile Transcellular Sarcomeric Network to Regulate Apical Cell Junctions and Tissue Geometry Current Biology, 23 (8), 731-736 DOI: 10.1016/j.cub.2013.03.039 
Copyright ©2013 Elsevier Ltd. All rights reserved.

May 6, 2013

Our bodies have multiple fronts for battling viruses, and it’s impressive that any of those suckers manage to invade our bodies at all.  When virus particles do make their way into a cell, it’s important for biologists to understand their pathway through a cell in order to create drug therapies and vaccines.  Today’s image is from a paper describing the use of high resolution imaging to understand this process.

The polarized cells that line our digestive and respiratory tracts form a tight barrier that protects our bodies from viruses.  Understanding how viruses are able to breach these polarized epithelial cells is important in guiding the development of therapeutics and vaccines, yet previous research has focused mainly on in vitro studies of virus entry into nonpolarized cells.  Microscopy advances have recently allowed the high-resolution imaging of virus entry in polarized epithelial cells.  Boulant and colleagues used live-cell spinning-disk confocal microscopy to follow the uptake of single mammalian reovirus (MRV) virions and infectious subvirion particles (ISVPs) in polarized Madin–Darby canine kidney cells.  Both virus particles were internalized by clathrin-mediated endocytosis at the apical surface.  MRV virions reached early and late endosomes, while ISVPs escaped the endocytic pathway prior to reaching early endosomes.  In the images above, the tight-junction protein ZO-1 (red, left) shows the typical belt pattern surrounding the polarized cells (side views are also shown in the top and side strips).  The MRV cell surface receptor JAM-A (red, right) is localized near tight junctions and on the apical side of the cells.

Boulant, S., Stanifer, M., Kural, C., Cureton, D., Massol, R., Nibert, M., & Kirchhausen, T. (2013). Similar uptake but different trafficking and escape routes of reovirus virions and infectious subvirion particles imaged in polarized Madin-Darby canine kidney cells Molecular Biology of the Cell, 24 (8), 1196-1207 DOI: 10.1091/mbc.E12-12-0852

September 27, 2012

Organs are not just a messy mash-up of cells. Their formation is carefully and elegantly orchestrated, with influences from both outside and inside of the cells. Today’s image is from a paper using micropatterned cell culture trickery to show how cell confinement affects epithelial morphogenesis.

During the development of many organs, epithelial morphogenesis transforms cells into sheets of epithelial cells with a functional lumen. These epithelial cells are polarized—one side of the cell faces the inside, or lumen, while the other side faces away from the organ. The process during which a cell becomes polarized relies on several cues, some of which are from the outside physical environment of the cell. Tissue rigidity, water tension, and cell confinement all participate in regulating cell shape and development. A recent paper describes how cell confinement affects lumen formation, a key part of epithelial organ morphogenesis. Rodríguez-Fraticelli and colleagues used surfaces with adhesive micropatterns to simulate cell confinement, and found that cell confinement limits actin contractility around the periphery of the cell, which in turn affects lumen formation. In addition, centrosome positioning is regulated by cell confinement. As seen in the images above, cells in low confinement (right) positioned their centrosomes toward the periphery of the micropatterned area (gray circles), while cells in high confinement (left, middle) positioned their centrosomes (green, arrowheads) toward the side where lumen formation would take place. Bottom row of images shows the side-view (z-stack) of the cells in the top row.

Alejo E. Rodríguez-Fraticelli, Muriel Auzan, Miguel A. Alonso, Michel Bornens, & Fernando Martín-Belmonte (2012). Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis originally published in the Journal of Cell Biology, 198 (6), 1011-1023 DOI: 10.1083/jcb.201203075

August 6, 2012

Morphogenesis may be a big word, but the concept is simple and beautiful. Morphogenesis refers to how cells become shaped and organized into complete tissue or organs….and eventually an actual organism. Morphogenesis is what countless developmental biologists think about as they fall asleep, as they wake up, as they shower…how about that for obsession?! Today’s image is from a paper on epithelial morphogenesis—specifically the formation of tube structures in a liver.

Understanding how cells rearrange themselves into tissue structures is a main goal of developmental biology. Many structures rely on epithelial cells that line a lumen. For example, the tubular bile ducts of the liver are made of epithelial cells that both regulate the composition of bile and prevent leakage of bile along the tube. These epithelial cells are called cholangiocytes, and a recent paper paves the way towards understanding how these cells form the tube structures during development. In this paper, Senga and colleagues identified a transcription factor called grainyhead-like 2 (Grhl2) that regulates the size of a lumen surrounded by epithelial cells during development. Grhl2 upregulates claudin 3 and claudin 4, components of the tight junctions that provide a tight barrier between epithelial cells. Grhl2 also targets Rab25, which in turn increases claudin 4 levels and regulates its localization at tight junctions. As seen in the images above, expression of Grhl2 (bottom row) in cysts of liver progenitor cells causes rapid expansion of the lumen inside of the cysts without increasing the number of cells, compared with the slow formation of the lumen in a control cyst (top row).

Kazunori Senga, Keith E. Mostov, Toshihiro Mitaka, Atsushi Miyajima, & Naoki Tanimizu (2012). Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and Rab25 Molecular Biology of the Cell, 23 (15), 2845-2855 DOI: 10.1091/mbc.E12-02-0097

May 14, 2012

Transformers may have been the hot toy in the 80s and I definitely remember coveting my big brother’s collection, but they have nothing on the cool ability of cells to completely transform themselves. During epithelial remodeling, a polarized epithelial cell transforms itself into a migratory cell….they truly are “more than meets the eye” (“robots in disguise!” ptchoo ptchoo!). Today’s stunning images are from a paper describing the cytoskeletal changes that drive this transformation.

Epithelial remodeling is the transformation of an epithelial cell into a migratory cell, a process that occurs throughout development. Although it is known that dramatic cytoskeletal changes drive epithelial remodeling, it wasn’t previously understood how these changes occur in a three-dimensional tissue. Gierke and Wittmann recently used high resolution imaging of cultured 3D epithelial cysts to track cytoskeletal changes during morphogenesis. After triggering an epithelial-to-mesenchymal (migratory) transition in the cysts, Gierke and Wittmann found that the growth rate of microtubules increased prior to any visible changes in cell shape, and that microtubules reorganize and grow into cell extensions during epithelial remodeling. In addition, this microtubule reorganization requires the function of EB1, a protein that binds to the plus-end of growing microtubules and can regulate the interaction of microtubules with the cortex of the cell. The images above show cell extensions in cysts triggered to undergo an epithelial-to-mesenchymal transition (actin filaments are labeled). Control extensions (top row) continuously grow over time, with actin-rich lamellipodia at the tip. Without EB1 (bottom row), extensions lack a single actin-rich tip and instead have multiple protrusions that do not grow.

Gierke, S., & Wittmann, T. (2012). EB1-Recruited Microtubule +TIP Complexes Coordinate Protrusion Dynamics during 3D Epithelial Remodeling Current Biology, 22 (9), 753-762 DOI: 10.1016/j.cub.2012.02.069

 Copyright ©2012 Elsevier Ltd. All rights reserved

 

May 10, 2012

I’m an old fart…heck, I was born an old fart. So, you won’t be seeing me in da club. But if I ever go, I’ll be reassured knowing that bouncers kick the knuckleheads out and keep the crowd to a safe limit. Though they may be beefy tough guys, bouncers are clearly getting their cues from epithelial cells, which extrude both dying and healthy cells when overcrowded, according to a recent paper.

Cell extrusion is the process in which epithelial cells get rid of apoptotic, or dying, cells. By getting rid of dying cells, the epithelial sheet can maintain its tight barrier function for the tissue or organ. A recent paper shows that epithelial sheets can also extrude healthy, living cells. According to Eisenhoffer and colleagues, an epithelial sheet overcrowded with cells will extrude living cells in order to maintain tissue homeostasis. This mechanism was found in human, canine, and zebrafish epithelial cells, and could be induced by overcrowding epithelial cells in a stretched, then released, chamber in the lab. Cells are extruding in the images of human colon epithelial tissue above. A dying cell in the process of extruding (right) shows caspase-3 staining (green, arrow), a marker for apoptosis, while a living cell extruding (left, arrowhead) does not.

 

Eisenhoffer, G., Loftus, P., Yoshigi, M., Otsuna, H., Chien, C., Morcos, P., & Rosenblatt, J. (2012). Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia Nature, 484 (7395), 546-549 DOI: 10.1038/nature10999

Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

 

May 7, 2012

Phosphorylation serves as a molecular switch, and the combinations of different proteins phosphorylated or dephosphorylated at any given time is mind-numbing. Phosphorylation caused one of many “Holy crap, cells are amazing!” moments in college as I realized how the regulation within a cell can be so complex. Today’s image is from a study that looks at the regulation of phosphorylation of a polarity protein.

Protein kinase C (PKC) is a family of kinases, one of which is the well-studied polarity protein atypical PKC (aPKC). These kinases must be phosphorylated before their catalytic domain is activated. The protein PDK1 serves to phosphorylate and activate newly-made PKC proteins, and a recent paper reveals that it can also phosphorylate older PKC proteins that have been since dephosphorylated, seen as a “rescue” of activity. Mashukova and colleagues also found that PDK1 is localized in membrane compartments on the apical side of some epithelial cells in close proximity to intermediate filaments, suggesting a new signaling function in these membrane compartments (endosomes). In the images above, epithelial cells have PDK1 (red) localized to the apical pole of the cells, where intermediate filaments (green) are found.

Mashukova, A., Forteza, R., Wald, F., & Salas, P. (2012). PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia Molecular Biology of the Cell, 23 (9), 1664-1674 DOI: 10.1091/mbc.E11-12-0988

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 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

March 12, 2012

If it walks like a duck and quacks like a duck, it must be a duck….or it could be me doing my best duck impression. Scientists don’t like to make assumptions, but instead are driven to painstakingly test the cellular unknowns. Today’s image is from a paper that serves as a good example of how assumptions may not be accurate, but instead lead to a fascinating story that prompts more questions.

Desmosomes are cell-cell adhesion structures that help tissues resist mechanical stress by connecting with the cells’ intermediate filament networks. The mechanical strength provided by desmosomes is well documented in tissues such as heart muscle and stratified epithelia (skin, esophagus, etc). The intestine is a simple epithelial tissue that contains desmosomes, and as it is under a lot of mechanical stress from the movement and content of digesting food, it can be easily assumed that the desmosomes in intestinal tissue provide mechanical support. Not so, according to a recent paper by Sumigray and Lechler. The desmosomal protein desmoplakin (DP) is not essential for cell adhesion or tissue integrity in intestinal epithelia, nor is it necessary for proper organization of keratin intermediate filaments. However, DP is important for the structure of microvilli, the actin-rich structures that provide surface area for the absorption of nutrients. As seen in the images above, the microvilli of intestinal cells from DP knockout mice (middle, right) are shorter and misshapen when compared to wild-type cells (left).

Sumigray, K., & Lechler, T. (2012). Desmoplakin controls microvilli length but not cell adhesion or keratin organization in the intestinal epithelium Molecular Biology of the Cell, 23 (5), 792-799 DOI: 10.1091/mbc.E11-11-0923

January 26, 2012

There are so many images that are in our collective memory…images that mark historic and significant events. There are the photos of Tiananmen Square, the “Migrant Mother” from the Great Depression, Abbey Road, etc. Well, cell biologists have our own images that stick in our collective memory. One of those more recent images is the “Svitkina image” of actin filaments, which I’ve mentioned before. So, when I saw that the Svitkina lab published a paper recently, I knew I had to share!

Cell-cell junctions are crucial for development, tissue structure, and cell-cell communication. One type of cell-cell junction is the adherens junction (AJ), which is a cadherin-based junction that links to the actin cytoskeleton within the cell. Although AJs are well-studied structures, how they assemble is still not completely known. A recent paper looks at the underlying actin filaments in developing AJs. According to Hoelzle and Svitkina, a junction is formed first by neighboring cells’ lamellipodia, sheet-like membrane extensions. Next, the two cells are connected by cadherin on thin bridges that look similar to filopodia, which are finger-like actin projections. Interestingly, these bridges form by actin filament growth from the rear-side of the lamellipodia towards the cell periphery. The images above are transmission electron micrographs of actin filaments in a bridge that connects two different cells (each cell labeled a different color in middle image). Gold beads (yellow, right image) found at the far ends of each cell’s bridge label VASP proteins, which are markers for filopodia.

Hoelzle, M., & Svitkina, T. (2011). The cytoskeletal mechanisms of cell-cell junction formation in endothelial cells Molecular Biology of the Cell, 23 (2), 310-323 DOI: 10.1091/mbc.E11-08-0719

January 12, 2012

For a little protein, the cell is a big place. Many times it’s necessary for proteins to be clustered together in order to get a job done. Today’s image is from a paper describing how E-cadherin gets clustered at adherens junction sites like a flock of 12-year old teeny-bopper girls at a Twilight movie.

Sheets of epithelial cells are polarized—one side of the epithelial sheet faces the inside/lumen of an organ or tissue, while the other attaches to a supportive basement membrane. The establishment and polarization of epithelial cells depends on adherens junctions (AJs), protein complexes that serve as cell-cell junction sites. AJs are composed of a transmembrane protein called E-cadherin that connects the junctions to the cell’s actin cytoskeleton. E-cadherin must be distributed on the cell’s plasma membrane for AJ assembly, but how it is brought to the membrane and/or clustered at certain sites is not fully understood. A recent paper finds an association between E-cadherin and the exocyst protein Exo70. The exocyst is a complex that brings proteins from the Golgi apparatus (where they are sorted) to the plasma membrane. According to Xiong and colleagues, Exo70 is required for E-cadherin clustering at the plasma membrane and for maturation of newly-formed AJs. Exo70 performs this feat through its association with a kinase that can interact directly with E-cadherin (PIPKIγ, for you membrane-junkies out there). As seen in the images above, this kinase (green) and Exo70 (red) both associate at the lateral membranes of epithelial cells, where AJs form. Top row shows the cells as if we are looking down onto the cells, while bottom row shows cells as if we were looking through the plane of cells.

Xiong, X., Xu, Q., Huang, Y., Singh, R., Anderson, R., Leof, E., Hu, J., & Ling, K. (2011). An association between type I PI4P 5-kinase and Exo70 directs E-cadherin clustering and epithelial polarization Molecular Biology of the Cell, 23 (1), 87-98 DOI: 10.1091/mbc.E11-05-0449

November 14, 2011

Just like Willy Wonka’s trained squirrels getting rid of the bad nuts, an epithelial sheet is able to push out a dying or unwanted cell, all while maintaining an intact barrier. Today’s image is from a paper describing how the direction of cell extrusion is regulated, and is from the same lab that provided a cell extrusion image featured earlier this year (check it out here).

When a cell is extruded from an epithelial sheet, it can be pushed either apically, into the lumen of the organ, or basally, further into the underlying tissue surrounding the organ. This direction is important—although most extruded cells are eliminated on the apical side, living cells that are extruded basally may affect development or become an invading cancerous cell. A recent paper describes results showing that the tumor suppressor protein APC can target microtubules to the cell base in order to drive apical extrusion. In addition, this function of APC is required in the cell that is being extruded, in turn controlling the direction of the actin contractions that squeeze the cell out of the epithelial sheet. Cells either without APC or with a mutated form of APC extruded on the basal side. In the images above, microtubules (green) in wild-type epithelial cells (left) are highly organized and oriented towards the cell being extruded (asterisk). In APC mutant epithelial cells (right), microtubules are reduced and disorganized around the extruding cell.

Marshall, T., Lloyd, I., Delalande, J., Nathke, I., & Rosenblatt, J. (2011). The tumor suppressor adenomatous polyposis coli controls the direction in which a cell extrudes from an epithelium Molecular Biology of the Cell, 22 (21), 3962-3970 DOI: 10.1091/mbc.E11-05-0469

August 11, 2011

“Our country is just so polarized these days,” I say as I shake my fist, then tell those pesky kids to get off of my lawn. “Polarized” doesn’t have to be a dirty word…in fact, if it weren’t for polarized epithelial cells we’d all be big puddles of cells lacking the ability to digest food, reproduce, circulate blood, or breathe. Today’s image is from a paper describing how septins guide microtubule organization in polarized epithelial cells.

Epithelial cells form sheets that line various organs throughout the body. These epithelial sheets are polarized, meaning the cells are not symmetrically organized. For example, our intestine is lined with a polarized epithelial sheet that must absorb nutrients from the intestine’s cavity in one side of the cell sheet, and then eventually guide those nutrients to blood vessels. A key step in the polarization of a cell is the organization of the microtubule cytoskeleton. Microtubules are organized in a radial array in rounded cells, while the microtubules in polarized epithelial cells are arranged along the lateral borders of the cells and in networks under the apical and basal membranes (top and bottom). A recent paper looks at the role of proteins called septins in guiding microtubule organization during the establishment of polarity. Septins are filamentous proteins known for their roles in cell polarity, but Bowen and colleagues were able to show a functional link between septins and microtubule organization. Specifically, two populations of septins allow microtubule growth, bundling, and capture in different regions of the cell. In the image above, thick septin filaments (left, green in merged) are seen colocalized with microtubules (middle, red in merged) in epithelial cells. Bottom images are higher magnification views of the boxed region.

Bowen, J., Hwang, D., Bai, X., Roy, D., & Spiliotis, E. (2011). Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia originally published in The Journal of Cell Biology, 194 (2), 187-197 DOI: 10.1083/jcb.201102076

July 7, 2011

Totally tubular! If Bill and Ted had an excellent adventure in the human body, you can be certain that they’d learn about the most excellent tube structures throughout the body. From the veins that carry our blood to the branching tubules in our lungs, tubes are very important structures. A recent paper looks at the role of adhesion proteins during tubule formation.

During development, dramatic rearrangements of epithelial sheets results in the formation of branched tubules, as seen in kidney, lung, and mammary gland tissue. As one might expect, these rearrangements require coordination of several cellular events such as cell division, migration, polarization, and adhesion. A recent paper describes the role of two adhesion proteins, E-cadherin and cadherin-6, in tubule formation. Jia and colleagues found that cadherin-6 is important in inhibiting tubule formation, while E-cadherin is important in the formation of a tubule’s lumen (its inside cavity). Images above show the use of cell cysts as a model for epithelial tubule and lumen formation, with fluorescent tags showing a lateral marker (blue) and lumen-facing apical markers (green and red). Samples of control cysts, cysts without cadherin-6, E-cadherin, or both are shown (moving left to right). Although the mutant cysts appear abnormal, polarization was not disrupted in cysts without either cadherin (although multiple lumens are visible in cysts lacking E-cadherin). The polarization of cysts lacking both cadherins, however, was completely disrupted.

Jia, L., Liu, F., Hansen, S., ter Beest, M., & Zegers, M. (2011). Distinct roles of cadherin-6 and E-cadherin in tubulogenesis and lumen formation Molecular Biology of the Cell, 22 (12), 2031-2041 DOI: 10.1091/mbc.E11-01-0038

June 30, 2011

Between the high number of breast cancer patients and the pink ribbons seen all over, breast health is and will always be a hot topic. The breast is a fascinating system of different cell and tissue types, and today’s image is from a paper looking at a population of epithelial cells in the breast.

Breast tissue contains two layers of epithelial sheets—an outer layer of myoepithelial cells (MECS) and an inner layer of luminal epithelial cells (LECs). The LECs greatly expand during certain events, such as pregnancy and tumorigenesis, which results in either thinner or discontinuous coverage by the outer layer of MECs. Because of this, the MEC layer serves as an epithelial “gatekeeper,” by generating boundaries that help organize breast tissue. A recent paper looks at this gatekeeper function of MECs and finds that two proteins, SLIT and ROBO2, are important in regulating the proliferation of MECs. And, in turn, the growth of the MEC layer regulates the branching of mammary tissue. Image above shows mammary tissue in normal (left) or Robo mutant (right) mice. The loss of Robo leads to excessive branching (close-up views of boxed regions on bottom).

Macias, H., Moran, A., Samara, Y., Moreno, M., Compton, J., Harburg, G., Strickland, P., & Hinck, L. (2011). SLIT/ROBO1 Signaling Suppresses Mammary Branching Morphogenesis by Limiting Basal Cell Number Developmental Cell, 20 (6), 827-840 DOI: 10.1016/j.devcel.2011.05.012
Copyright ©2011 Elsevier Ltd. All rights reserved.

May 26, 2011

“Bring out yer dead!” Thankfully, epithelial sheets have a much more efficient and beautiful way of clearing out dying cells than the famous Monty Python scene. Today’s stunning images are from a paper describing the signaling epithelial cells use to push out dying cells. It’s no wonder that the authors’ image made the cover of Journal of Cell Biology!

The function and health of an organ strongly depends on the integrity of the epithelial sheet protecting it. In order to preserve the epithelial barrier, dying cells are pushed out of the epithelial sheet in a precise and finely-tuned process called apoptotic cell extrusion. In this event, cells surrounding the dying, apoptotic cell form an actin and myosin ring that contracts to push the dying cell out of the sheet. A recent paper describes the signaling that takes place to initiate cell extrusion. The dying cell produces a signal called bioactive lipid sphingosine-1-phosphate (S1P), which activates actin-myosin contraction via its receptor (S1P2) in neighboring cells. The images above show epithelial sheets in normal and S1P2 mutant zebrafish larvae. In the mutant, the apoptotic cell (green) stays in the epithelial sheet and lacks the actin ring (red) seen in the wild-type tissue.

Gu, Y., Forostyan, T., Sabbadini, R., & Rosenblatt, J. (2011). Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway originally published in The Journal of Cell Biology, 193 (4), 667-676 DOI: 10.1083/jcb.201010075

November 29, 2010

Basic research is fundamental if we want to make strides in understanding disease. Please (politely) shout this from the mountaintops and make sure your lawmakers and funding agencies understand this. Today’s image is from a paper that investigates a key player in cell scattering, which is an event very similar to cancer metastasis.

Cell scattering is a term used to describe cell-cell dissociation and migration and occurs in liver development, organ regeneration, and metastasis. Cell scattering is induced by hepatocyte growth factor/scatter factor (HGF/SF1), and a recent paper describes similar cell scattering after a block to the protein α₅β₁ integrin, which is a receptor mediating the attachment of the cell to the surrounding extracellular matrix. In addition, blocking the function of this integrin triggers changes in expression of other proteins that mediate adhesion and migration. Image shows control (top) or integrin-blocked (bottom) liver progenitor cells. After a functional block to integrin function, cells are scattered and have decreased levels of E-cadherin (green), which is important in cell-cell adhesion of epithelial cells. Nuclei are in blue.

Vellón, L., Royo, F., Matthiesen, R., Torres-Fuenzalida, J., Lorenti, A., & Parada, L. (2010). Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells BMC Cell Biology, 11 (1) DOI: 10.1186/1471-2121-11-81

November 15, 2010

Cell biologists make amazing discoveries using cells grown flat on culture dishes, yet the cells in an organism grow and function in three dimensions. Some cell biologists use clever tricks to understand how cells function in three dimensions by using cells cultured in gels, and they find out very valuable information.

Throughout biology there are many cases of oriented cell division, during which a cell orients the mitotic spindle on a specific axis. These cell divisions can occur throughout development in stem cell divisions, tissue morphogenesis, and epithelial sheet formation. Epithelial sheets are monolayers of polarized cells, and cells must divide within the plane of the sheet in order to maintain the monolayer. A recent paper uses cultured mammalian cells grown as cysts as a model for epithelial cell divisions, and describes the important role of a protein called Pins in ensuring that cell divisions are oriented correctly. Hao and colleagues found that the correct localization of Pins on the surface of epithelial cells is regulated by the Par3 and aPKC polarity proteins. Images above are of cysts with (left) or without (right) Par3. While the wild type cyst has one lumen facing the apical surface of cells (green), cysts without Par3 form multiple lumens.

Hao, Y., Du, Q., Chen, X., Zheng, Z., Balsbaugh, J., Maitra, S., Shabanowitz, J., Hunt, D., & Macara, I. (2010). Par3 Controls Epithelial Spindle Orientation by aPKC-Mediated Phosphorylation of Apical Pins Current Biology, 20 (20), 1809-1818 DOI: 10.1016/j.cub.2010.09.032
Copyright ©2010 Elsevier Ltd. All rights reserved.