July 24, 2014


How many times can you say the word “gonad” in a sentence without giggling? If the answer is none, then I congratulate you on turning thirteen. If the answer is many, then you must be a biologist. Biologists appreciate the value of a good gonad, and so should you. The gonad of the worm C. elegans serves as an important model in which to study tissue organization and development, as you’ll see in the paper that accompanies today’s image.

At the end of cell division, cytokinesis typically results in two separate daughter cells. Some cytokinesis, though, is incomplete and leads to two daughter cells sharing cytoplasm. This shared cytoplasm, or syncytium, can be found in the germ cells of many species from worms to humans. The germline of the worm C. elegans is a polarized tube in which germ cells are arranged around the shared cytoplasmic core and move along a conveyer belt of oocyte production. Amini and colleagues recently reported on the formation of the syncytial C. elegans germline throughout development, and the role of the short Anillin family scaffold protein ANI-2. ANI-2 is localized to the intercellular bridges that connect the germ cells to the shared cytoplasm, and loss of ANI-2 results in destabilization of intercellular bridges and sterility. The defects seen in worms lacking ANI-2 are likely due to a loss of the stability and elasticity of the intercellular bridges that is required to compensate for the stress of cytoplasmic streaming during oogenesis. Images above show the germlines of wild-type and ani-2(-) worms at different larval stages (membranes in green; nuclei in red). Worms lacking ANI-2 have abnormal multinucleated germ cells (arrowheads).

Amini, R., Goupil, E., Labella, S., Zetka, M., Maddox, A., Labbe, J., & Chartier, N. (2014). C. elegans Anillin proteins regulate intercellular bridge stability and germline syncytial organization originally published in the Journal of Cell Biology, 206 (1), 129-143 DOI: 10.1083/jcb.201310117

July 18, 2014

Poor polar bodies typically go the way of that old container of Chinese take-out in your fridge and are eventually dumped. Thanks to a very clever study published in Cell, polar body transfer can prevent the transmission of inherited mitochondrial diseases. Waste not, want not.

The meiotic divisions of an oocyte result in the production of an egg in the extrusion of two very small polar bodies. These polar bodies have the same genetic material as the egg but have only a small number of organelles, including mitochondria. The DNA of mitochondria (mtDNA) can carry mutations that cause a variety of diseases. As mtDNA is maternally inherited due to the abundance of mitochondria in the oocyte, recent studies have focused on the replacement of mutant mtDNA with normal mitochondria to treat these inherited diseases. A recent paper tests the use of polar bodies as the source of donor genomes in a potential new method for mitochondrial replacement. As polar bodies have the same genome as the egg, but does not have mtDNA variants, they can successfully replace the genome in a recipient egg that already has normal mtDNA. Wang and colleagues have shown that polar body genome transfer successfully does just this, and provides a potential new therapy for preventing inherited mitochondrial diseases. The images above show the presence of mitochondria (red) in oocytes and polar bodies. Both polar bodies (PB1 and PB2) have far fewer mitochondria than the ooctyes.

Wang, T., Sha, H., Ji, D., Zhang, H., Chen, D., Cao, Y., & Zhu, J. (2014). Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases Cell, 157 (7), 1591-1604 DOI: 10.1016/j.cell.2014.04.042
Copyright ©2014 Elsevier Ltd. All rights reserved.

July 10, 2014

Do your thoughts and feelings have colors? Do you feel red with rage during traffic, or green with envy when your lady swoons over Ryan Gosling? A recent methods paper introduces a very cool technique that allows the visualization and measurement of voltage within an excited neuron.

Biologists build tools that are ideally accurate, fast, and non-damaging to the cells and organisms on which they are used. In a recent paper in Nature Methods, Hochbaum and colleagues describe the improved technique for simultaneous imaging of neuron stimulation and the resulting action potentials. Hochbaum and colleagues engineered a vector, called Optopatch, that uses their actuator (CheRiff) to induce action potentials and their voltage indicators (QuasAr1 and QuasAr2) to visualize and measure membrane voltage. Optopatch allows the measurement of action potentials on a microsecond timescale, without the need for electrodes. In the images above, a neuron expressing Optopatch shows action potential propagation (left to right, arrow is site of action potential initiation).

Hochbaum, D., Zhao, Y., Farhi, S., Klapoetke, N., Werley, C., Kapoor, V., Zou, P., Kralj, J., Maclaurin, D., Smedemark-Margulies, N., Saulnier, J., Boulting, G., Straub, C., Cho, Y., Melkonian, M., Wong, G., Harrison, D., Murthy, V., Sabatini, B., Boyden, E., Campbell, R., & Cohen, A. (2014). All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins Nature Methods DOI: 10.1038/nmeth.3000
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

June 30, 2014

Which came first, the primordial germ cell or the gamete? Unlike the old chicken or egg philosophical dilemma, we know for certain that the primordial germ cell came first. And, thanks to a recent paper about primordial germ cells in sea urchins, we now know that they can migrate across the urchin embryo.

During development, germ cells produce gametes (eggs or sperm). In many organisms, including mammals, primordial germ cells (PGCs) are born far from the eventual location of gametes and must migrate across the embryo while dividing. In sea urchins, small cells called micromeres are PGCs and precisely segregate along the left-right axis of the embryo. A recent paper by Campanale and colleagues describes the use of live-cell imaging of small micromeres in urchin embryos to test whether the precise segregation of these eight micromeres is due to passive translocation or active migration. Images show that the micromeres are, in fact, motile cells with features such as cortical blebs and filopodia that direct migration across the sea urchin embryo, towards the coelomic pouches. In the images above, sea urchin embryos express micromere (red) and apical membrane (green) markers before (left) and during (middle, right) gastrulation.

Campanale, J., Gökirmak, T., Espinoza, J., Oulhen, N., Wessel, G., & Hamdoun, A. (2014). Migration of sea urchin primordial germ cells Developmental Dynamics, 243 (7), 917-927 DOI: 10.1002/dvdy.24133

June 19, 2014

As the widespread therapeutic use of stem cells moves closer to reality, I just fasten my seatbelt a little tighter. An exciting time for stem cells and their scientist stalkers, a recent paper shows the regeneration of damaged monkey hearts by human embryonic stem cell-derived cardiomyocytes.
 

Human embryonic stem cells (hESCs) can be programmed to differentiate into countless different cell types. hESCs are already being tested in humans to treat retinal diseases and spinal cord injuries. hESCs can be differentiated into cardiomyocytes, or heart muscle cells, to potentially repair a damaged heart after injury or failure. In a recent study, Chong and colleagues used hESC-derived cardiomyocytes (hESC-CMs) to repair injured monkey hearts, which are more comparable to human hearts in size and number of cardiomyocytes required. After first developing techniques for producing large, clinical-scale cryopreserved batches of hESC-CMs, Chong and colleagues found that these cells successfully re-muscularized the injured monkey hearts. The electromechanical coupling between host heart tissue and hESC-CM graft tissue was successful, yet non-fatal arrhythmias were observed. In the images above, host vessels (red) extend into graft tissue (white, boxed region and higher magnification below) and are able to successfully perfuse the graft tissue.

Chong, J., Yang, X., Don, C., Minami, E., Liu, Y., Weyers, J., Mahoney, W., Van Biber, B., Cook, S., Palpant, N., Gantz, J., Fugate, J., Muskheli, V., Gough, G., Vogel, K., Astley, C., Hotchkiss, C., Baldessari, A., Pabon, L., Reinecke, H., Gill, E., Nelson, V., Kiem, H., Laflamme, M., & Murry, C. (2014). Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts Nature, 510 (7504), 273-277 DOI: 10.1038/nature13233
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

June 10, 2014

The Life History of a Single Kinetochore Fiber sounds like a book a lot of us would enjoy (well, me at least). It isn’t really a book about a plucky kinetochore fiber who triumphs over a difficult childhood, but rather the focus of a fascinating recent paper. In this paper published in Molecular Biology of the Cell, LaFountain and Oldenbourg present results showing a model for kinetochore microtubule formation that occurs at kinetochores.

Kinetochore fibers link chromosomes to the mitotic spindle, which drives chromosome segregation during anaphase. The prevailing model of kinetochore fiber formation includes a “search and capture” mechanism, in which some dynamic spindle microtubules reach a kinetochore and become stabilized by the interaction. A recent paper by LaFountain and Oldenbourg shows, however, that the maturation of these kinetochore fibers depends on the addition of microtubules at the kinetochore-proximal end, with polymerization towards the spindle pole. In this study, the naturally birefringent microtubules of crane-fly spermatocytes were examined, allowing a quantitative analysis of where microtubules are added. In the images above, kinetochore-proximal addition of microtubules can be seen in the centrosome-free half-spindle (red arrows) of a crane-fly spermatocyte, from early prometaphase to metaphase (top to bottom).

LaFountain, J., & Oldenbourg, R. (2014). Kinetochore-driven outgrowth of microtubules is a central contributor to kinetochore fiber maturation in crane-fly spermatocytes Molecular Biology of the Cell, 25 (9), 1437-1445 DOI: 10.1091/mbc.E14-01-0008

April 30, 2014

Have you ever driven in the wrong direction on a one-way street. It feels as wrong as a hamburger smoothie and you feel overwhelmed with panic. It’s important to go the right direction on one-way streets, and a neuron understands this. Neurons are polarized so that signals can come and go in the right direction. Today’s stunning image is from a paper describing the cytoskeletal architecture within a region of a neuron that’s important for polarity. 

The axon initial segment (AIS) is the part of an axon closest to the neuron’s cell body, and is the site of action potential initiation. The AIS is crucial for the neuron’s polarity, which facilitates the direction of incoming signals (coming in from dendrites) and outgoing information (out along the axon to the synapse). A recent study from Jones and colleagues investigated how the AIS maintains neuronal polarity. Jones and colleagues used platinum replica electron microscopy (PREM) to image the cytoskeleton in hippocampal neurons, and found that it begins with a bundle of microtubules. A dense fibrillar–globular coat covers this microtubule bundle and contains many proteins as well as actin filaments. Actin filaments are found in two sparse populations—either stable, short filaments or dynamic, long filaments. Jones and colleagues propose that the dynamic actin filaments play a role in the AIS coat, while the stable filaments may play a structural role in the AIS diffusion barrier. This diffusion barrier prevents the mixing of plasma membrane components from dendrites and axons, an important factor in maintaining polarity. The image above shows microtubules within the AIS, with thin fibrils (arrows) and a fibrillar coat over the microtubules (arrowheads) visible.

Jones, S., Korobova, F., & Svitkina, T. (2014). Axon initial segment cytoskeleton comprises a multiprotein submembranous coat containing sparse actin filaments originally published in the Journal of Cell Biology, 205 (1), 67-81 DOI: 10.1083/jcb.201401045