November 30, 2012

I didn’t pay enough attention to primary cilia in my earlier years, and that is one of life’s big regrets (well, regret is a strong word). They are very fascinating little sensory organelles, and the thought of primary cilia carrying the weight of neuron migration on their little basal body shoulders is impressive. Check out today’s image, from a paper showing the role of primary cilia in brain development.

Neurons are frequently born far from their final home in the brain, and this migration is key to healthy nervous system development and function. A recent paper shows the importance of primary cilia in the migration of interneurons (neurons that connect one neuron to another) in the cerebral cortex. Primary cilia are microtubule-based sensory organelles that project out of a cell’s membrane. Higginbotham and colleagues imaged migrating interneurons in the developing cerebral cortex and found a correlation between primary cilia dynamics and interneuron mobility. This process requires the ciliary protein Arl13b, a GTPase in the Arf/Arl family. Arl13b ensures correct localization and movement of guidance cue receptors in primary cilia. In the images above, interneurons (green chamber in cartoon, green cells in images) migrate along tracks toward a signal secreted by dorsal cortical cells (blue chamber in cartoon). The migration of Arl13b mutant interneurons (right panel) was drastically reduced when compared to control interneurons (left, same scale).

Higginbotham, H., Eom, T., Mariani, L., Bachleda, A., Hirt, J., Gukassyan, V., Cusack, C., Lai, C., Caspary, T., & Anton, E. (2012). Arl13b in Primary Cilia Regulates the Migration and Placement of Interneurons in the Developing Cerebral Cortex Developmental Cell, 23 (5), 925-938 DOI: 10.1016/j.devcel.2012.09.019
Copyright ©2012 Elsevier Ltd. All rights reserved.

November 27, 2012

We have a ton of neurons. And each of those neurons has many dendrites. And each dendrite has countless little dendritic spines. Thinking about how complex one single neuron is in order to receive a signal from another cell gives me an identity crisis. What if we are all just little dendritic spines on our universe’s neuron?! Was that stupid stampede for Walmart’s Black Friday sale worth it for those folks? Was my self-restraint when faced with leftover pumpkin pie worth it? Is any of it worth it?!

Dendritic spines are small actin-rich protrusions on a neuron’s dendrite, the structure that receives information from other neurons. The morphology and density of the dendritic spines can be regulated by neurotransmitters, actin dynamics, and actin-regulating proteins. The neuron-specific actin regulator cortactin-binding protein 2 (CTTNBP2) regulates the formation and maintenance of dendritic spines, and is even associated with autism spectrum disorder. A recent paper investigates the role of a CTTNBP2 homologue, CTTNBP2NL (CTTNBP2 N-terminal-like protein). Chen and colleagues found that while CTTNBP2 expression is found in the brain, CTTNBP2NL is not. In addition, CTTNBP2NL does not appear to play a role in dendritic spine formation. Although both CTTNBP2 and CTTNBP2NL associate with cortactin, a well-studied actin regulator, CTTNBP2 is associated with the cell’s cortex while CTTNBP2NL is found on actin stress fibers. In addition, Chen and colleagues found a link between CTTNBP2 and the protein phosphatase 2A (PP2A) complex, specifically with CTTNBP2 targeting the PP2A complex to dendritic spines. In the images above, cells show labels for cortactin (red) and actin fibers (blue). CTTNBP2NL (green, top) associates with stress fibers (arrows), while CTTNBP2 (green, bottom) is distributed around the cortex (arrowheads).

Chen, Y., Chen, C., Hu, H., & Hsueh, Y. (2012). CTTNBP2, but not CTTNBP2NL, regulates dendritic spinogenesis and synaptic distribution of the striatin-PP2A complex Molecular Biology of the Cell, 23 (22), 4383-4392 DOI: 10.1091/mbc.E12-05-0365

Small World

Every year, Nikon hosts the Small World competition, which pits stunning microscopy images against one another for oooohs and aaaahs from around the world.  The images are breathtaking, for both scientists and lay-folk alike

So, to kick off a brief Thanksgiving break, I wanted to send you all to the 2012 winners of the Small World competition, announced a few weeks ago.  Click here for the Small World winners and honorable mentions...and lose an afternoon to image browsing, microscope jealousy, and pride in the amazing advances within the microscopy field. 

Happy Thanksgiving, everyone!  Thanks for reading HighMag!

November 12, 2012

When you were still developing, your brain was an overachiever just like that straight-A class president with perfect teeth and a canned food drive. Your brain overproduced neurons, then later paired down the neuron population to fine-tune development and function. Today’s image is from a paper that describes this process and the regulation behind it.
 
Interneurons are neurons that make connections with other neurons, and are found throughout our bodies. In our brain, our cortical neurons are produced far away from their final destination in the fully mature brain. It has been suggested that these neurons are overproduced, and then migrate to the cortex where the excess neurons are eliminated. A recent paper shows this process occurring in developing mice. Southwell and colleagues showed this developmental cell death occurring within the developing mouse brain, within laboratory cultures, and within cortical neurons transplanted into a developing mouse brain. Their results suggest that the cell death is triggered cell-autonomously (from within the cell) or triggered due to competition between other interneurons for survival signals. The image above shows interneuron precursor cells cultured on a plate of cortical feeder layers containing neurons (green), astrocytes (red), and oligodendrocytes (white). About 30% of the cortical interneurons cultured on these feeder layers later underwent cell death.

Southwell, D., Paredes, M., Galvao, R., Jones, D., Froemke, R., Sebe, J., Alfaro-Cervello, C., Tang, Y., Garcia-Verdugo, J., Rubenstein, J., Baraban, S., & Alvarez-Buylla, A. (2012). Intrinsically determined cell death of developing cortical interneurons Nature, 491 (7422), 109-113 DOI: 10.1038/nature11523
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

November 9, 2012

Size really does matter, folks! Ask any scientist about the potential uses for nanoparticles, and you’ll quickly agree that these tiny little suckers deserve a spot at your dinner table, complete with cute nano-plates and nano-forks. Today’s image is from a paper describing a clever use of nanoparticles to systematically monitor how cells respond to force.

A cell encounters force from its entire environment. A cell responds to mechanical force by regulating signals, development, and migration, among other things. Biologists have been trying to understand how cells respond to force for years, and clever techniques have included manipulation by optical tweezers, micropipettes, and atomic force microscopy. These techniques, however, have been limited by their ability to monitor one cell at a time. A recent paper describes a technique in which many cells respond to uniform forces on the cortex. In this study, Tseng and colleagues plated cells on micropatterned magnetic substrates. Magnetic nanoparticles within the cells were then manipulated by a magnetic field in order to apply a uniform mechanical force on the cell cortex. By monitoring large numbers of individual cells under these forces, Tseng and colleagues developed a way for biologists to have higher control and accuracy in understanding how force affects cells. The images above show representative images of cells under varying amounts of force. The dose of nanoparticles (blue) in each cell (increasing from bottom to top) and strength of the magnetic field (increasing from left to right) both affect the response from cells. A higher nanoparticle dose and magnetic field gradient caused cells to produce more filopodial membrane extensions from cells (actin is in green) from the region where the force was applied.

Tseng, P., Judy, J., & Di Carlo, D. (2012). Magnetic nanoparticle–mediated massively parallel mechanical modulation of single-cell behavior Nature Methods, 9 (11), 1113-1119 DOI: 10.1038/nmeth.2210
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

November 6, 2012

It is Election Day here in the US, which means that some of us need stress relief until the results are tallied. So, maybe you can imagine the graceful membrane dynamics of a cell and let their lava-lamp-like groove lull you into a happy place. Today’s image is from a paper describing the regulation of caveola biogenesis.

Caveolae are small invaginations on a cell’s plasma membrane that play important roles in cell signaling and endocytosis (the uptake of material into a cell). Caveolae depend on proteins called caveolins, but the details of caveola biogenesis are not completely understood. A recent paper describes results showing the importance of phosphorylation of Caveolin-1 (Cav1) in the formation of caveolae. Phosphorylation is the addition of a phosphate group to a protein, which functions as a molecular switch to change the protein’s activity. Joshi and colleagues found that the phosphorylation of Cav1 induces a feedback loop that links together mechanical stress on the cell, caveola biogenesis, and focal adhesion regulation at the cell’s membrane. These results place Cav1 on a list of critical proteins that help a cell respond to mechanical stress. In the images above, mutations of Cav1 that mimic phosphorylation (Cav1Y14R and Cav1Y14D) cause the formation of more caveolae and caveolae clusters (arrows and asterisks) than control cells (Cav1WT).

Joshi, B., Bastiani, M., Strugnell, S., Boscher, C., Parton, R., & Nabi, I. (2012). Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation originally published in the Journal of Cell Biology, 199 (3), 425-435 DOI: 10.1083/jcb.201207089

November 2, 2012

Despite being a scientist, sci-fi/fantasy is just not my cup of tea. Sometimes, though, I am positive that a scientific name is really some Klingon starship or Game of Throne character. Ever since I learned about the nodes of Ranvier in high school biology, I have been sure that they’re really from some fantasy world. Today’s image is from a paper that doesn’t really dispel my confusion...the concept of measuring and understanding high nerve conduction velocity in teeny tiny axons is other-worldly. 

Myelin is a material that forms a layer around the axon of a neuron. Schwann cells wrap around axons and produce these myelin sheaths, which are spaced between gaps called the nodes of Ranvier. The main purpose of myelin is to allow nerve impulses to move very quickly along the axon, but the relationship between nerve conduction velocity and the distance between myelin sheaths was unclear. Recently, Wu and colleagues measured conduction velocity in mice with Schwann cells carrying a mutation that prevented elongation of Schwann cells. In these cells with short Schwann cells, and in turn short distances between nodes of Ranvier, conduction velocity dropped and motor function of the mice was impaired. As these mice developed and the internodal distance increased, nerve conduction velocity and motor function recovered. Wu and colleagues suggest that the high conduction speed reached by increasing internodal distance reaches a “flat maximum.” Above, cross-sections of nerves in mice at 3 (top) or 24 (bottom) weeks old show some differences in myelin between normal mice (left column) and mice with a Schwann cell elongation mutation (right column). 24-week old mutants show some myelin folds and some structures indicative of demyelination and remyelination (arrowheads, bottom right).

Wu, L., Williams, A., Delaney, A., Sherman, D., & Brophy, P. (2012). Increasing Internodal Distance in Myelinated Nerves Accelerates Nerve Conduction to a Flat Maximum Current Biology, 22 (20), 1957-1961 DOI: 10.1016/j.cub.2012.08.025

Copyright ©2012 Elsevier Ltd. All rights reserved.