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