October 28, 2014

If you’ve ever tried to get your kids to share a donut, you understand the importance to dividing things equally (and learning crucial lessons…just buy more donuts next time...I mean, seriously!). Cell division is no different—chromosomes and organelles must all get divided equally. Today’s images are from a paper showing how mitochondria are positioned during cell division in order to allow equal segregation.

Many years of research have focused on the equal segregation of chromosomes during cell division. Organelles such as mitochondria must also be segregated equally in a dividing cell, and errors in this process can lead to disease. A recent paper identifies the actin motor Myosin-XIX (Myo19) as a key player in mitochondrial partitioning during cell division. Myo19 is localized to mitochondria, and cells depleted of Myo19 have an abnormal distribution of mitochondria. Rohn and colleagues found that cells lacking Myo19 experience stochastic division failure, suggesting that mitochondria are physically preventing successful cell division. The images above show dividing cells labeled to visualize mitochondria (green) and the mitotic spindle (red) in control cells (top two rows) and cells depleted of Myo19 (bottom two rows). Without Myo19, mitochondria moved towards spindle poles at the onset of anaphase, causing an asymmetric distribution at division when compared with control cells.

BONUS!! Here is a rotating 3D reconstruction of an A549 stained to visualize microtubules (green), mitochondria (red), and DNA (blue). Omar Quintero, HighMag friend and a co-author from today’s paper, loves this image: “I like it because it reminds me of the scenes in StarWars where the Rebels are planning their attack on the Death Star.”

Rohn, J., Patel, J., Neumann, B., Bulkescher, J., Mchedlishvili, N., McMullan, R., Quintero, O., Ellenberg, J., & Baum, B. (2014). Myo19 Ensures Symmetric Partitioning of Mitochondria and Coupling of Mitochondrial Segregation to Cell Division Current Biology DOI: 10.1016/j.cub.2014.09.045

Copyright ©2014 Elsevier Ltd. All rights reserved.

January 31, 2013

I like to think of early embryos as kicking ass and asking questions later.  Once fertilization happens, embryos undergo rapid, synchronous cell divisions.  Next, the cell divisions slow down as cells begin to move around and form the different germ layers, then organs, within the growing embryo.  Today’s image is from a paper describing this transition in fruit flies, and how gene transcription in the embryo plays a role.

In fruit fly embryos, early development begins with synchronous nuclear divisions, which are divisions in which the nuclei divide without going through cytokinesis.  After 13 rounds of mitosis, the large multinucleate syncytium pauses in cycle 14 and undergoes cellularization to form plasma membranes around nuclei.  During this transition, the transcription of the embryo’s own genes begins as the maternally-contributed genetic material (RNA) is degraded.  A recent paper describes evidence that this switch to zygotic transcription is the trigger for the pause in cycle 14 and cellularization.  Sung and colleagues found a novel mutation in the RNPII215 gene that results in a reduced number of nuclear divisions, as well as premature zygotic transcription and cellularization.  The number of nuclear divisions in this mutant depends on zygotic transcription and Vfl, a transcription factor that controls many early zygotic genes.  In the images above, a mutant early fly embryo (bottom) has fewer cells due to the reduced nuclear divisions, compared to a normal embryo (top).  A nuclear protein is in green, and the pair-rule protein Eve is in red.

Sung, H., Spangenberg, S., Vogt, N., & Großhans, J. (2013). Number of Nuclear Divisions in the Drosophila Blastoderm Controlled by Onset of Zygotic Transcription Current Biology, 23 (2), 133-138 DOI: 10.1016/j.cub.2012.12.013
Copyright ©2013 Elsevier Ltd. All rights reserved. 

June 18, 2012

I love chromosomes. I am always in awe when I see these little things that are chock full of information and instructions for a cell, and in turn, a whole organism. When I think about how finely-tuned the dance is that allows chromosome segregation to happen correctly every time during mitosis, I am beyond impressed. Today’s image is from a paper describing how sister chromatids become bound to one another.

Sister chromatids remain held together until anaphase segregates them into two future daughter cells during mitosis. Chromatid cohesion is mediated by the cohesin complex of proteins and is established long before mitosis. A recent study identified the role of a protein called XEco2 in acetylating a cohesin complex member called Smc3, a step that is required for the establishment of chromatid cohesion. In addition, Higashi and colleagues found that this role of XEco2 is important prior to DNA replication, requiring the formation of the pre-replication complex. Later, DNA replication serves to stabilize cohesion between sister chromatids. In the images above, sister chromatids are bound together in control cells and in cells depleted of XEco1 (left two columns). In cell depleted of XEco2, XEco1 and XEco2 together, or cohesin (middle and right two columns), sister chromatids are not bound tightly to one another.

Higashi TL, Ikeda M, Tanaka H, Nakagawa T, Bando M, Shirahige K, Kubota Y, Takisawa H, Masukata H, & Takahashi TS (2012). The Prereplication Complex Recruits XEco2 to Chromatin to Promote Cohesin Acetylation in Xenopus Egg Extracts. Current biology : CB, 22 (11), 977-88 PMID: 22560615

Copyright ©2012 Elsevier Ltd. All rights reserved.

 

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

February 27, 2012

Yeast is magical. It gives our bread and beer its deliciousness, and provides biologists with a fantastic tool for understanding cell biology. Many of our monumental cell biology discoveries were due to yeast, so please whisper a heartfelt “Thank you” to yeast the next time you enjoy a beer. Today’s image is from a paper describing the structure of the septin network required for cell division in yeast.

Many yeast species divide by budding – a mother cell replicates its genome within its nucleus while a small bud forms and grows. The nucleus divides and the bud splits off of the mother cell. This split between mother and bud, or cytokinesis, depends on structural proteins called septins. Although the structure and function of septins has been studied for years, exactly how they are arranged at the bud neck of dividing yeast was not clear. Despite the small size of the bud neck, Bertin and colleagues recently imaged septin ultrastructure in dividing yeast cells by using improved techniques of electron microscopy that allow better preservation of membranes, combined with three-dimensional reconstruction of images. Specifically, Bertin and colleagues found septin filaments that ran both parallel and perpendicular to the mother-bud axis. In the images above, a view of the bud neck near the top of the membrane (top) shows circumferential filaments (green arrows). In a deeper view of the bud neck (bottom), filaments that follow the contour of the bud neck (next to red lines) can be seen, as well as a cross-sectional view of the circumferential filaments (green arrows).

Bertin, A., McMurray, M., Pierson, J., Thai, L., McDonald, K., Zehr, E., Garcia, G., Peters, P., Thorner, J., & Nogales, E. (2011). Three-dimensional ultrastructure of the septin filament network in Saccharomyces cerevisiae Molecular Biology of the Cell, 23 (3), 423-432 DOI: 10.1091/mbc.E11-10-0850

January 19, 2012

One of the first things you likely learned in your high school biology class was about cyclins, and their elegant and important discovery about 30 years ago. Cyclins are well-studied proteins that (you guessed it) cycle throughout the cell cycle and guide progress from one stage to the next. Today’s image is from a paper showing novel roles for a cyclin, and serves as a great reminder that no matter how much we may know about something, there are always new and exciting things to discover.

A cell must coordinate more than a handful of processes in order for cell division to occur correctly, and a group of proteins called cyclins helps to guide this process. Cyclin levels cycle throughout the cell cycle and activate kinases called Cdks, and together the cyclin-Cdk complexes trigger specific events. A recent paper discusses new results showing how a cyclin (Cyclin A2) regulates cytoskeletal organization and cell migration, independently of its binding to Cdk. According to Arsic and colleagues, depletion of Cyclin A2 causes a change in the distribution of actin filaments and an increase in cell migration. Cyclin A2 interacts with and activates RhoA, an actin regulator, which in turn negatively regulates migration. In addition, metastatic cancer cells show less Cyclin A2 expression than non-spreading tumor cells. In the images above, the distribution of actin (red) and focal adhesions (structures that link the cell to the underlying matrix, green) changes when Cyclin A2 is depleted (bottom row), when compared to control cells (top row).

Arsic, N., Bendris, N., Peter, M., Begon-Pescia, C., Rebouissou, C., Gadea, G., Bouquier, N., Bibeau, F., Lemmers, B., & Blanchard, J. (2012). A novel function for Cyclin A2: Control of cell invasion via RhoA signaling originally published in The Journal of Cell Biology, 196 (1), 147-162 DOI: 10.1083/jcb.201102085

June 27, 2011

In my grad school days, I was an asymmetric cell division aficionado. I loved the asymmetric cell division that I studied for those years, the one-cell stage worm embryo. With that statement out of the way, I can admit that I secretly coveted the extremely asymmetric divisions of ooctyes. Check out today’s lovely image of a mouse oocyte, from the cover of Current Biology.

Rather than dividing to produce two identical daughter cells, an oocyte divides to produce a large egg ready for fertilization and a very small polar body. This extreme asymmetric division allows the egg to retain all of the crucial cytoplasm to support a future early embryo. This asymmetry is necessary for fertility and development, but the mechanisms required for this event are not completely understood. A recent paper describes the importance of two novel actin nucleators called Spire1 and Spire2 in mouse meiotic divisions. These Spire proteins drive the assembly of an actin network that acts as a substrate for positioning of the meiotic spindle, and promotes the cytokinetic cleavage furrow that results in polar body extrusion. Image above shows a mouse oocyte undergoing a meiotic division—chromosomes are cyan, microtubules are blue, and cortical actin is red.

BONUS!! Check out this great movie showing spindle positioning in normal (left) and Spire-deficient (right) ooctyes.

To see the cover of Current Biology for this issue, which features the above image, click here.

Pfender, S., Kuznetsov, V., Pleiser, S., Kerkhoff, E., & Schuh, M. (2011). Spire-Type Actin Nucleators Cooperate with Formin-2 to Drive Asymmetric Oocyte Division Current Biology DOI: 10.1016/j.cub.2011.04.029
Copyright ©2011 Elsevier Ltd. All rights reserved.

March 24, 2011

Cancer cells have taught biologists about a lot of wacky things that can happen when things don’t go merrily along for a cell. Entosis is a process in which a living cell is internalized into a neighboring cell, and has been found to occur in some tumors. A recent paper describes exactly what can go wrong here.

Aneuploidy refers to a cell having an incorrect number of chromosomes, and is a feature of many cancers. Typically, aneuploidy occurs from a failure in cytokinesis, the physical division of a cell after mitosis, due to misregulation or mutation of genes involved in cell division. Sometimes, however, aneuploidy can occur from a non-genetic failure of cytokinesis, according to a recent paper. In this paper, Krajcovic and colleagues look at cytokinesis failures due to entosis, a process in which living cells are internalized by their neighboring cells. These cell-in-cell structures are found in some tumors, and the outer “host” cell is frequently aneuploid. This aneuploidy occurs when the internalized cell physically disrupts the constriction required to cleave two cells during cytokinesis, as seen in the images above. Cytokinesis of the cell-in-cell structure (left) is not going well compared with a normal cell (right). Red labels (and in black and white insets) mark active constriction during cytokinesis, and should be symmetric around the cells. The mitotic spindle is labeled in green, and chromosomes in blue.

BONUS!! Movie of above cell, attempting cytokinesis, can be found here. More cool movies from this paper can be found here.

Krajcovic, M., Johnson, N., Sun, Q., Normand, G., Hoover, N., Yao, E., Richardson, A., King, R., Cibas, E., Schnitt, S., Brugge, J., & Overholtzer, M. (2011). A non-genetic route to aneuploidy in human cancers Nature Cell Biology, 13 (3), 324-330 DOI: 10.1038/ncb2174
Adapted by permission from Macmillan Publishers Ltd, copyright 2011

March 3, 2011

When I first learned about the elegant experiments of the late Ray Rappaport, I remember feeling like I was having a Zen moment. Amazing things can be learned from some of the simplest experimental designs, and this is a very calming and satisfying concept. Today’s image is from a paper using those same sea urchin eggs that Rappaport used*, and provides us with a great prediction tool for determining how a cell will divide.

Many cells in an embryo must divide in a certain orientation, and many biologists have tried to make predictions on how this orientation is determined. Add the varying shapes a cell may take on within a developing organism, and making these predictions is less than straightforward. In order to make predictions on cell division orientation, a group of biologists set sea urchin eggs into wells of varying shapes. By monitoring the cell division axis in many cells set in wells of many shapes, Minc and colleagues developed a computational model that predicts how the cell division axis is determined for any given shape. Images above show sea urchin embryos in wells of different shapes.

Minc, N., Burgess, D., & Chang, F. (2011). Influence of Cell Geometry on Division-Plane Positioning Cell, 144 (3), 414-426 DOI: 10.1016/j.cell.2011.01.016
©2011 Elsevier Ltd. All rights reserved.

* Correction: Rappaport didn't use sea urchin eggs. In most of his experiments, he used a different echinoderm--the sand dollar. Thanks to Bob G. for the note!