August 29, 2014

Stem cells in adults are responsible for tissue renewal and many cancers. So, the hunt for stem cells is important and has already been successful, with stem cell populations identified in countless types of tissues. Stem cells in the ovary, however, were shy to show themselves until a recent study using a marker for the Wnt protein Lgr5.

In adults, stem cells are responsible for maintaining homeostasis during normal wear and tear of a tissue. The ovary and its ovary surface epithelium (OSE) experience remodeling during adulthood, yet stem cells of the ovary have been hard to find. A recent paper by Ng and colleagues describes the identification of stem cells in the ovary using markers for the Wnt target protein Lgr5. Lgr5 marks stem cells in several epithelial tissues. Ng and colleagues identified Lgr5+ cells in the mouse ovary starting from ovary organogenesis and lasting into adulthood. Using lineage tracing, Ng and colleagues confirmed that Lgr5+ cells are, in fact, stem cells that contribute to development, homeostasis, and repair of the OSE and associated structures. In the images above, Lgr5+ cells (green) are visible in embryonic (left) and postnatal (middle, right) ovarian tissue.

Ng, A., Tan, S., Singh, G., Rizk, P., Swathi, Y., Tan, T., Huang, R., Leushacke, M., & Barker, N. (2014). Lgr5 marks stem/progenitor cells in ovary and tubal epithelia Nature Cell Biology, 16 (8), 745-757 DOI: 10.1038/ncb3000
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

August 26, 2014

If you have little ones in your house, you might assume that the phrase “randomly fluctuating forces” is referring to your home. This phrase actually refers to the background force in a cell coming from active and motor-driven cell processes. Today’s image is from a study that developed a way to measure these forces. 

Actin- and microtubule-based motors move many types of material around a cell to drive critical cellular events. These motor-driven movements and other active processes in the cell contribute to a background of fluctuating forces in a cell. These stochastic forces collectively drive random motion of organelles and proteins within a cell, in turn affecting the dynamics and metabolic state of a cell. To measure these forces, Guo and colleagues developed force spectrum microscopy (FSM) to directly quantify the fluctuating forces in a cell’s cytoplasm, specifically by measuring the movements of individual injected particles. Guo and colleagues found that these forces are strong enough to move both large and small components, and that malignant cells have a higher level of fluctuating forces compared to benign cells. Image above shows a cell with injected particles (green), with the 2-minute trajectories (black) superimposed.

Guo, M., Ehrlicher, A., Jensen, M., Renz, M., Moore, J., Goldman, R., Lippincott-Schwartz, J., Mackintosh, F., & Weitz, D. (2014). Probing the Stochastic, Motor-Driven Properties of the Cytoplasm Using Force Spectrum Microscopy Cell, 158 (4), 822-832 DOI: 10.1016/j.cell.2014.06.051
Copyright ©2014 Elsevier Ltd. All rights reserved.

August 21, 2014

Microtubules are known for their fascinating dynamics, but some cellular processes require a more stable microtubule cytoskeleton. Thankfully, these stable, acetylated microtubules are just as photogenic as their non-modified microtubule pals. Today’s image is from a paper describing the role of the protein paxillin in microtubule acetylation. 

Crawling cells require coordination of adhesive forces, cytoskeletal rearrangements, and cell polarization. Cell polarization helps to direct newly synthesized proteins to the leading edge of the crawling cell, relying on both a stable microtubule cytoskeleton and positioning of the Golgi apparatus in front of the nucleus. The stability of these long-lived microtubules is due to acetylation—a post-translational modification of α-tubulin. A recent study by Deakin and Turner uncovered a role for the focal adhesion scaffolding protein paxillin in regulating microtubule acetylation, which in turn regulates Golgi integrity and cell polarization. Paxillin modulates microtubule stability through its inhibition of HDAC6, an α-tubulin deacetylase, and does so in both normal and transformed cells. In the images above, depletion of paxillin (bottom) in malignant (left column) and normal (right column) cell types resulted in a drop of microtubule acetylation (yellow), compared to control cells (top).

Deakin, N., & Turner, C. (2014). Paxillin inhibits HDAC6 to regulate microtubule acetylation, Golgi structure, and polarized migration originally published in the Journal of Cell Biology, 206 (3), 395-413 DOI: 10.1083/jcb.201403039

August 19, 2014

Think of life without tubes for a moment. Not only would our huge bodies cease to exist, but our homes’ plumbing would be a mess and my 5-year old’s marble run would be pretty boring. The formation of tubes during development is a fascinating topic. Today’s image is from a paper describing the role of endocytosis in seamless tube formation.

The trachea of the fruit fly is a simple tubular system that functions as the respiratory system of the fly. The star-shaped tracheal terminal cells form seamless tubes that extend the length of long cellular extensions. Schottenfeld-Roames and colleagues recently published a study investigating the mutations in the braided gene. Tracheal terminal cells in braided mutants have tubular cysts and fewer branches, as seen in the images above (top is wild-type; bottom is mutant). braided encodes Syntaxin7, a endocytosis protein that promotes fusion of vesicles to early endosomes. Schottenfeld-Roames and colleagues found that mutations in other early endosome proteins cause similar terminal cell tube defects. Additional data showing increased levels of the apical protein Crumbs in braided terminal cells suggests that early endocytosis regulates levels of Crumbs, which in turn affects tube formation through actin cytoskeleton modulation. The images above show the luminal membrane (green) and an apical protein (magenta) in tracheal tubes. The tubes in braided mutants are cystic and abnormal, and the tube tips are disorganized (higher magnified views of the boxed regions are on the left).

Schottenfeld-Roames, J., Rosa, J., & Ghabrial, A. (2014). Seamless Tube Shape Is Constrained by Endocytosis-Dependent Regulation of Active Moesin Current Biology, 24 (15), 1756-1764 DOI: 10.1016/j.cub.2014.06.029
Copyright ©2014 Elsevier Ltd. All rights reserved.

All the images were acquired by Dr. Jodi Schottenfeld-Roames.

August 14, 2014

Astrocytes used to be the red-headed stepchild of the neurobiology world, but no more! Once considered to be just filler material, astrocytes are now known to function in the development and function of synapses, though the mechanisms are unclear. Today’s stunning image is from a paper showing how astrocytes can stabilize synapses, possibly serving as an important component of learning and memory. 

The synapses of neurons in the central nervous system are dynamic in response to learning and memory. The synapses are enveloped by perisynaptic astrocytic processes (PAPs), which are intricate processes of astrocytes. This close association of PAPs with synapses suggests an important role for astrocytes in synaptic development, transmission, and plasticity—the focus of a recent paper by Bernardinelli and colleagues. In this study, time-lapse imaging of brain slices revealed that long-term potentiation increased PAP motility and astrocyte coverage of the synapse. In vivo imaging of the somatosensory cortex of adult mice after whisker stimulation showed an increase in PAP motility, and later dendritic spine stability. From these results, Bernardinelli and colleagues identify a novel bidirectional interaction between PAPs and synapses, in which synaptic activity regulates PAP plasticity, which in turn regulates PAP coverage of synapses and long-term spine survival. The image above shows CA1 neurons (green) and stratum radiatum astroctyes (red) in mouse hippocampal tissue.

Bernardinelli, Y., Randall, J., Janett, E., Nikonenko, I., König, S., Jones, E., Flores, C., Murai, K., Bochet, C., Holtmaat, A., & Muller, D. (2014). Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability Current Biology, 24 (15), 1679-1688 DOI: 10.1016/j.cub.2014.06.025
Copyright ©2014 Elsevier Ltd. All rights reserved.

August 7, 2014

No matter how many brilliant discoveries are made by countless brilliant scientists, there will always be a lot of unknowns out there. These unknowns are what keep our mental wheels turning, our imaginations running, and our labs busy. Today’s image is from a paper that describes a newly-discovered process of vascular development called “canalogenesis.”

Schlemm’s canal (SC) is a flattened tube that encircles the anterior portion of the eye and drains fluid from the area. Abnormal drainage contributes to glaucoma, a disease that causes vision loss, yet a description of SC development and SC endothelial cells (SECs) is incomplete. In a recent study, Kizhatil and colleagues developed a new whole-mount procedure and used high-resolution confocal microscopy to study large regions of the SC during development. Kizhatil and colleagues found that the phenotype of SECs is a blend of blood and lymphatic endothelial cells, and that the SC develops through by a newly-discovered process called “canalogenesis.” Canalogenesis has features that are similar to, yet different from, the three well-studied vascular development programs—vasculogenesis, angiogenesis, and lymphangiogenesis. The image above was acquired using the new whole-mount procedure that protects the delicate ocular drainage structures. The SC (blue) is visualized in 3D relative to nearby blood vessels (magenta).

Kizhatil, K., Ryan, M., Marchant, J., Henrich, S., & John, S. (2014). Schlemm's Canal Is a Unique Vessel with a Combination of Blood Vascular and Lymphatic Phenotypes that Forms by a Novel Developmental Process PLoS Biology, 12 (7) DOI: 10.1371/journal.pbio.1001912