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
If you are a mitotic spindle aficionado or superfan, then you understand how the mitotic spindle has a life of its own. Information on the spindle’s composition, dynamics, and list of duties can fill entire volumes…and there is still so much we are learning about the spindle. Today’s image is from a paper that adds another chapter in our metaphorical mitotic spindle book.
The mitotic spindle is composed of dynamic microtubules and countless proteins that ensure chromosomes are equally segregated into identical daughter cells at the end of cell division. Because much of the structure of the spindle comes from the cytoplasm, the contributions from the nucleus have remained unclear. A recent paper identifies the long-elusive presence of a nuclear matrix—a viscous matrix of proteins that supports the formation and function of the spindle. The nuclear matrix is composed of nuclear proteins that reassemble after nuclear envelope breakdown into a pole-to-pole structure. By looking at the cell divisions in fruit flies, Yao and colleagues found that the nuclear matrix is distinct from spindle microtubules, and is found closely around chromosomes following drug treatments that depolymerized microtubules. The time-lapse images above show mitosis in the syncytial Drosophila embryo. The nuclear matrix (green, Chromator) has a spindle-like morphology as the microtubule spindle (red, tubulin) itself forms.
Yao C, Rath U, Maiato H, Sharp D, Girton J, Johansen KM, & Johansen J (2012). A nuclear-derived proteinaceous matrix embeds the microtubule spindle apparatus during mitosis. Molecular biology of the cell, 23 (18), 3532-41 PMID: 22855526
Once an egg finds its dance partner, the incredible changes that take place have fascinated biologists for centuries. These changes are kicked off immediately, and thanks to modern microscopy we get to see them up close. Today’s image is from a paper describing actin-mediated changes at the membrane of an egg shortly after fertilization.
Shortly after fertilization, actin assembly and dynamics drive changes in membrane physiology in the egg. One of these changes is an increase in efflux from the egg, or transport out of the egg, at the same time that short actin-based protrusions called microvilli are assembled around the egg. A recent paper investigates this link between efflux and microvilli after fertilization of sea urchin eggs. Whalen and colleagues found that a protein called ABCB1a translocates to the tips of microvilli shortly after fertilization. ABCB1a is an ABC transporter, a family transmembrane proteins that drive movement of various material into and out of many cell types. By using structured illumination microscopy (3D-SIM), Whalen and colleagues captured high-resolution images of actin filaments shortly after fertilization, and found movement of ABCB1a along growing actin filaments. Both efflux activity and movement of ABCB1a to microvilli tips were inhibited after actin polymerization was blocked. The images above show actin filaments (green) and ABCB1a (red) at different time points shortly after fertilization. By 60 minutes after fertilization, ABCB1a moved from below microvilli to the tips of the protrusions.
Kristen Whalen, Adam M. Reitzel, & Amro Hamdoun (2012). Actin polymerization controls the activation of multidrug efflux at fertilization by translocation and fine-scale positioning of ABCB1 on microvilli Molecular Biology of the Cell, 23 (18), 3663-3672 DOI: 10.1091/mbc.E12-06-0438
It’s hard to not get excited about stem cells and their potential. The advances that will likely take place due to stem cells (and already have!) couldn’t have been dreamed up by even George Jetson’s creators. (Side note: where’s my flying car and robot housekeeper?!) Today’s image is from a paper showing the success of stem cells in healing a spinal cord injury.
Stem cells are unspecialized cells able to differentiate into various other cell types throughout development and adulthood. The prospect of using stem cells in treating diseases or repairing traumatic injuries drives the research of many biologists. A recent paper describes how stem cells can repair a spinal cord injury in mice. Lu and colleagues grafted mouse neural stem cells onto the sites of severe spinal cord injuries, and found that these cells differentiated into different cell types, including neurons. These neurons projected long axons that were able to form synapses with host neurons, and allowed functional recovery of the spinal cord. Human stem cells exhibited similar growth within the injured spinal cords of mice. The images above show the site of an injured spinal cord, several weeks after the injury. Neural stem cells (green) were able to grow and completely fill in the injured area.
Copyright ©2012 Elsevier Ltd. All rights reserved.
Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, & Tuszynski MH (2012). Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell, 150 (6), 1264-73 PMID: 22980985
I’m sure you've been here before….you’re at a family gathering, and some distant relative or in-law hears that your research involves worms, flies, or yeast. You are snidely asked what use it is to do research on that, and then asked what kind of job you could actually get with that kind of background. This happened to me (at a funeral), but I didn’t have either the speed or the smugness to rattle off the list of diseases understood or medications developed thanks to these kinds of organisms. Next time, I’ll just pass out a copy of the paper that today’s image comes from—booyah!
Throughout evolution, many genes are coopted for use in diverse organisms. Recently, the gene network that maintains the cell wall in yeast, a fungus, was discovered to also play a role in vertebrate angiogenesis. Angiogenesis is the growth of blood vessels from pre-existing vessels, and is an important step in transforming a tumor into a spreading, malignant cancer. The same research group that realized this yeast-angiogenesis link suggested that drugs affecting the yeast cell wall may also function as angiogenesis inhibitors for chemotherapy. Cha and colleagues found that an inexpensive antifungal drug called thiabendazole could block angiogenesis in animal models and human cells. Specifically, the drug disassembles newly-sprouted blood vessels. When Cha and colleagues grafted human tumors into mice, they found that thiabendazole treatment slowed tumor growth and limited growth of the vascular network. In the images above, the network of blood vessels in a Xenopus frog embryo is disrupted after thiabendazole treatment (bottom), compared to a wild type embryo (top).
Cha HJ, Byrom M, Mead PE, Ellington AD, Wallingford JB, & Marcotte EM (2012). Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent. PLoS biology, 10 (8) PMID: 22927795
If I had to describe myself as a cell, I would want to say something about being a fired-up neuron, or a nurturing nurse cell, or a chameleon stem cell. Realistically, though, I’d be a muscle fiber—painfully organized and precise. When things aren’t so organized I’d just be a twitching little muscle cell until my closet was organized by sleeve length, my pantry in alphabetical order, my various to-do lists organized by priority. A recent paper describes how the nuclei and organelles within a muscle fiber are so regularly spaced (but sadly does not describe any suggestions for my own personal organization).
Striated muscle fibers have densely packed myofibrils, which are the structures that make muscle contractions happen. The muscle fiber is a large multinucleated cell, meaning that there are more than one nucleus. These nuclei, as well as other organelles, must be evenly distributed along the length of the fiber. KASH domain proteins play a role in positioning nuclei and other organelles in various cell types, and a recent paper found that two KASH proteins play this role in muscle cells in the fruit fly. Elhanany-Tamir and colleagues found that these two proteins, called Klar and MSP-300, cooperate to ensure the even spacing of nuclei within a muscle fiber. These two proteins link a nuclear ring of MSP-300 to astral microtubules. Without either of these KASH proteins, the nuclear spacing is irregular. MSP-300 also is important in the spacing of other organelles—mitochondria and ER—within the muscle fiber. In the images above, muscle fibers from wild-type (left), msp-300 mutant, and klar mutant fruit fly larvae are stained for MSP-300 (red) and a nuclear marker (green). In the mutants, the MSP-300 nuclear ring (arrowheads) is dissociated from the nucleus.
Elhanany-Tamir H, Yu YV, Shnayder M, Jain A, Welte M, & Volk T (2012). Organelle positioning in muscles requires cooperation between two KASH proteins and microtubules. originally published in the Journal of Cell Biology, 198 (5), 833-46 PMID: 22927463
Next time you are cursing your yard for having to prune your bushes, just take a cold sip of lemonade and know that you are helping your shrubs thrive. Or, you are just making them all look like green meatballs, like my shrubs. Win-win! Pruning is an essential part of development, and a recent paper shows pruning of the vasculature in the developing zebrafish brain.
Our brains are surrounded by a complex network of blood vessels that deliver oxygen and nutrients to the neurons. Although the existence of this vasculature has long been appreciated and studied, it has not been clear how the network is formed during development. A recent paper uses confocal live imaging to track the development of the vessel network in the developing zebrafish midbrain. Chen and colleagues found that the zebrafish brain undergoes both blood vessel growth and pruning during development. Blood vessel pruning is driven by blood flow—decreased blood flow triggers pruning, while increased blood flow impairs pruning. In the images above, a segment of blood vessel from the midbrain vasculature undergoes pruning (red arrow).
Chen Q, Jiang L, Li C, Hu D, Bu JW, Cai D, & Du JL (2012). Haemodynamics-driven developmental pruning of brain vasculature in zebrafish. PLoS biology, 10 (8) PMID: 22904685
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
