February 26, 2013

Change is good.  This mantra isn’t good for just uptight type-As like me, but for embryos too.  Morphogenesis describes the physical changes that shape an organism out of a ball of cells, and is at the center of countless obsessions and questions of developmental biologists.  Today’s image is from a paper that helps us understand how a sheet of cells can form three-dimensional structures.

Morphogenesis describes the physical transformation and organization of cells into the shape of a developing organ or organism.  In the developing fruit fly egg, the epithelial layer of cells surrounding the egg chamber develops two dorsally projecting tubes, in which appendages used for gas exchange by the embryo form.  This transformation of a sheet of cells into a three-dimensional tube structure is not completely understood, but a recent paper describes the cell rearrangements involved.  Osterfield and colleagues used live imaging and three-dimensional reconstruction to show that the formation of the appendages is driven by epithelial sheet bending and a series of cell intercalations, which correlates with the localizations of myosin and the polarity protein Bazooka.  Using computational models, Osterfield and colleagues test how a pattern of line tensions in cell-cell edges in the epithelial sheet could drive three-dimensional changes.  The images above show fruit fly egg chambers during appendage formation (top row).  Three-dimensional reconstructions (bottom row) show the process from above (left) and the side (middle, right), with the arrow pointing to out-of-plane bending of the tissue.

Osterfield, M., Du, X., Schüpbach, T., Wieschaus, E., & Shvartsman, S. (2013). Three-Dimensional Epithelial Morphogenesis in the Developing Drosophila Egg Developmental Cell, 24 (4), 400-410 DOI: 10.1016/j.devcel.2013.01.017 
Copyright ©2013 Elsevier Ltd. All rights reserved.

September 4, 2012

Membranes are not just cute little jackets that cells wear to keep them protected. Membranes are no joke—they are dynamic hotspots of action, and their composition plays a key role in many cellular processes. Today’s image is from a paper describing the composition of a cell’s plasma membrane during cell morphogenesis.

The cell’s plasma membrane serves as the entryway and exit for material and plays an important role in cell signaling. Although all plasma membranes are made of a bilayer of lipids, those lipids can vary depending on the type of cell. The local composition of lipids in the plasma membrane can affect cellular processes, as seen in the human pathogenic fungus human C. albicans. C. albicans can grow using a filamentous protrusion called a hypha, which was recently found to have an asymmetric distribution of lipids. According to Vernay and colleagues, the growth of the hyphal filament was accompanied by a gradient of the phospholipid PI(4,5)P2 (phosphoinositide bis-phosphate). PI(4,5)P2 is frequently found within membranes at the sites of polarized growth, trafficking, and actin reorganization. Vernay and colleagues found that the sharp gradient of PI(4,5)P2 is essential for proper cell morphogenesis of C. albicans, and depends on the actin cytoskeleton and PI(4)P synthesis. In the images above, hyphal filaments show a gradient of PI(4,5)P2 using a color-coding of PI(4,5)P2 signal (key shows relative levels). Highest PI(4,5)P2 levels are seen at the tips of the filaments.

Aurélia Vernay, Sébastien Schaub, Isabelle Guillas, Martine Bassilana, & Robert A. Arkowitz (2012). A steep phosphoinositide bis-phosphate gradient forms during fungal filamentous growth originally published in the Journal of Cell Biology, 198 (4), 711-730 DOI: 10.1083/jcb.201203099

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 3, 2012

Where did you come from? Understanding the answer to this question helps you get a grasp on who you are currently, and who you are becoming. Whoa, that was deep…enough of that crap! A recent paper puts the psychotherapy treatment on cells in the developing heart and adds to our understanding of where they are from.

The change that takes place in a developing heart is astounding—a simple tube structure with a single layer of cardiac muscle cells called cardiomyocytes must develop into a complex adult structure. How the early cardiomyocytes divide and move around to form the adult heart is difficult to map out due to their dynamic behavior and their location in a tissue that is difficult to image. A recent paper describes the use of a recently-developed technology called Brainbow, in which different cells can be labeled with about 90 different colors. Using Brainbow techniques, Gupta and Poss were able to track the division and movement of individual cardiomyocytes in the developing zebrafish heart, and found that the cells expand the cardiac tissue in patches of various sizes and shapes. By using clonal dominance as a mechanism for tissue expansion, the process is reminiscent of stem cells. The image above shows the surface of the ventricular side of a developing heart, each color representing a different clonal patch that arose from a single cardiomyocyte.

Gupta, V.; Poss, K. (2012). Clonally dominant cardiomyocytes direct heart morphogenesis Nature, 484 (7395), 479-484 DOI: 10.1038/nature11045

Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

 

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

February 20, 2012

Full disclosure: today’s image is near and dear to me. Today’s image is from a paper written by members of my former graduate lab, with some very close friends as the co-first authors. This is not to say that this paper isn’t utterly fascinating with sparkling images and fantastic experiments designed by some of the brightest scientists around (enough superlatives for you?), because it is all of the above and more. I’m just disclosing my bias so if today’s post sounds like a love letter, you’ll let it slide.

During development, it is necessary for cells to change their shape—it allows cells and sheets of cells to form into specific structures and tissues. Apical constriction drives cell shape changes in many cell types by contracting the actin-myosin network on the apical side of the cell, causing that side of the cell to shrink. After apical constriction, cells are shaped more like wedges, and a whole sheet of apically constricting cells can result in dramatic changes. For example, apical constriction drives the folding and closing of neural plate cells to form the neural tube, which later becomes our brain and spinal cord. A recent paper looks at apical constriction during gastrulation in the worm embryo, at the start of which two cells on the outside of the embryo apical constrict and are internalized into the middle of the embryo. Roh-Johnson and colleagues found that the actin-myosin networks were dynamic and contracting long before the cells showed any type of shape change, functioning as a molecular “clutch.” The cells were internalized only after the actin-myosin contractions appeared to have been mechanically linked to the cell-cell contact zone. Roh-Johnson and colleagues found this same molecular clutch in apically constricting cells in the developing fruit fly, suggesting that this mechanism might be a key component of apical constriction across the board. The images above show two timepoints of a worm embryo in the process of internalizing the two cells at the start of gastrulation (bottom image is about 6 minutes after the top image). Green is myosin, red is membranes, and blue marks the surfaces of the internalizing cells. Image credit: Chris Higgins and Liang Gao.

BONUS!! Check out a fancy little blurb about this paper in The Scientist here (complete with movie!).

BONUS!! Do you like worms? Of course you do! Mosey over to the Goldstein Lab’s site for more movies here.

Roh-Johnson, M., Shemer, G., Higgins, C., McClellan, J., Werts, A., Tulu, U., Gao, L., Betzig, E., Kiehart, D., & Goldstein, B. (2012). Triggering a Cell Shape Change by Exploiting Preexisting Actomyosin Contractions Science DOI: 10.1126/science.1217869

March 21, 2011

How do cells organize themselves into vastly different tissues and organs during development? This is a fundamental question for developmental biologists, and thankfully amazing microscopy can let us see it all unfold (or fold, or zip, or contract, or converge, or invaginate, or…well, you get the point).

Morphogenesis is the physical shaping of an organism during development. Because of the dynamic nature of morphogenesis, it has been helpful for biologists to image these events while they are happening, rather than taking single snapshot images. A recent paper uses live imaging microscopy techniques to look at the fruit fly’s egg chamber, which elongates 1.7-fold during its development. This paper describes how the surface of the egg undergoes oscillations of contractions that are due to oscillations of myosin accumulation. These contractions lead to the elongation of the tissue. Image above shows the periodic pattern of myosin accumulation (red) at different developmental stages of egg chamber development, with cartoons (top) as a guide.

BONUS!! Movie of above image can be seen here. Many more movies from this paper can be found here.

He, L., Wang, X., Tang, H., & Montell, D. (2010). Tissue elongation requires oscillating contractions of a basal actomyosin network Nature Cell Biology, 12 (12), 1133-1142 DOI: 10.1038/ncb2124
Adapted by permission from Macmillan Publishers Ltd, copyright 2011

June 21, 2010

Morphogenesis is the process in which an embryo and its organs are shaped and formed, and is accomplished through organization of groups of cells into compartments. Prior to morphogenesis, cells are programmed to follow a specific cell fate, yet once morphogenesis begins there is typically little plasticity in the identities of the cells. However, a recent paper shows the reprogramming of certain cells during late morphogenesis of the fruit fly Drosophila, dependent on the JNK signaling pathway this is common to many species. Image above is a developing fly embryo undergoing dorsal closure, a well-studied example of morphogenesis during which cells stretch and zip up the tissue. Yellow cells are the “mixer cells” identified as being reprogrammable and able to cross compartment boundaries, while red and green cells intercalate to take their place during (top) and after (bottom) dorsal closure.

Reference: Melanie Gettings, Fanny Serman, Raphaël Rousset, Patrizia Bagnerini, Luis Almeida, Stéphane Noselli. Authors’ PLoS Biology paper can be found here.