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.

July 5, 2012

I’ve never run a marathon, but I’d imagine that it is a rollercoaster of feelings that finishes with a life “high” that is unbeatable. That’s how I feel when I read a paper from the journal Cell. They’re long, exhausting, sweat-inducing, and frequently some of the most rewarding paper-reading experiences a biologist can have. Today’s image is from a Cell paper that is so extensive in data, with a story that starts with protein localization and ends with a behavior study in mice.

Fibroblast growth factors (FGFs) are proteins that regulate several processes during development, such blood vessel growth and neurogenesis. A research group recently investigated the developmental role of FGF13, a growth factor believed to be connected to X-chromosome-linked mental retardation. Wu and colleagues found that FGF13 interacts with and stabilizes microtubules in cerebral cortical neurons during development. Through this interaction, FGF13 is required to polarize neurons—an event necessary for proper neuron migration and brain development. Finally, Wu and colleagues tracked the behavior of mice lacking FGF13, and found a reduced learning ability similar to that seen in X-chromosome-linked mental retardation patients. Images above show control (left) and FGF13-silenced (right) neurons in cerebral cortical slices. Without FGF13, neurons could not complete their radial migration in the tissue.

Wu QF, Yang L, Li S, Wang Q, Yuan XB, Gao X, Bao L, & Zhang X (2012). Fibroblast growth factor 13 is a microtubule-stabilizing protein regulating neuronal polarization and migration. Cell, 149 (7), 1549-64 PMID: 22726441

 Copyright ©2012 Elsevier Ltd. All rights reserved.

March 29, 2012

I think polar bodies are pretty cute. These little nubbins are products of meiotic division, and a simple testament to how amazing and clever a dividing cell (an oocyte, in this case) can be. Sure, polar bodies aren’t around for long, but I thank my own two long-lost polar bodies that let me have enough nutrients to survive. I hardly knew you, Atticus and Grover. Today’s image is from a paper describing anaphase in mouse oocyte divisions.

Meiosis is a special type of cell division that produces eggs and sperm. In mice, the meiotic spindle in the developing egg, or oocyte, is small and positioned in a very asymmetric location. This helps ensure that the nutrient- and organelle-rich cytoplasm stays with the daughter cell (the egg) that will later be fertilized and support early embryonic development. The other daughter of the division is the polar body, a small round structure that eventually is degraded. A recent paper describes results showing the sequence of anaphase events during mouse meiosis. In most cases of cell division, chromosome separation during anaphase is achieved by the shortening of kinetochore microtubules (termed anaphase A) and the lengthening of the entire meiotic spindle (anaphase B). In most cell divisions, anaphase A precedes anaphase B, yet Greg FitzHarris has shown that the reverse is true in mouse oocytes. Early anaphase B helps to determine the final size of the polar body. In addition, this early anaphase B spindle lengthening is triggered by the loss of tension on kinetochore microtubules, which occurs when cohesion between sister chromatids is lost. The images above are timepoints of anaphase in a mouse oocyte, with microtubules (grey) and chromosomes (green) labeled.

FitzHarris, G. (2012). Anaphase B Precedes Anaphase A in the Mouse Egg Current Biology, 22 (5), 437-444 DOI: 10.1016/j.cub.2012.01.041
Copyright ©2012 Elsevier Ltd. All rights reserved.

October 31, 2011

All storytellers want to tell their story all the way to its end. Imagine how unsatisfying most movies or books would be without their endings. What if Scout didn’t get to meet Boo Radley? How boring would The Sixth Sense be? How tragic would Toy Story 3 be?! In cell biology, telling a whole story in one paper, from protein to cell to animal, is a rare luxury given the time and difficulty of most techniques. Today’s image is from a paper with a well-rounded story about the role of a cell cycle protein in non-cell cycle-related business.

The cell cycle is driven forward by complexes made up of proteins called cyclins and cyclin-dependent kinases (Cdks). One cyclin called cyclin E functions in the G1 to S phase transition in the cell cycle, marking the start of DNA replication. Because of this role, cyclin E is typically found in only dividing cells. A recent paper describes the important role of cyclin E in non-dividing cells in the adult brain. In this paper, Odajima and colleagues found that cyclin E regulates synapse formation by inhibiting Cdk5. Cyclin E disruption in neurons causes the number of synapses and dendritic spines to drop. Finally, adult mice with cyclin E-deficient brains had impaired learning and memory. In the images above, non-dividing neurons from mouse brain show the presence of cyclin E (red) in both axons and dendrites, along with Cdk5. SynGAP and Synapsin I are post- and presynaptic markers.

Odajima, J., Wills, Z., Ndassa, Y., Terunuma, M., Kretschmannova, K., Deeb, T., Geng, Y., Gawrzak, S., Quadros, I., Newman, J., Das, M., Jecrois, M., Yu, Q., Li, N., Bienvenu, F., Moss, S., Greenberg, M., Marto, J., & Sicinski, P. (2011). Cyclin E Constrains Cdk5 Activity to Regulate Synaptic Plasticity and Memory Formation Developmental Cell, 21 (4), 655-668 DOI: 10.1016/j.devcel.2011.08.009
Copyright ©2011 Elsevier Ltd. All rights reserved.

June 30, 2011

Between the high number of breast cancer patients and the pink ribbons seen all over, breast health is and will always be a hot topic. The breast is a fascinating system of different cell and tissue types, and today’s image is from a paper looking at a population of epithelial cells in the breast.

Breast tissue contains two layers of epithelial sheets—an outer layer of myoepithelial cells (MECS) and an inner layer of luminal epithelial cells (LECs). The LECs greatly expand during certain events, such as pregnancy and tumorigenesis, which results in either thinner or discontinuous coverage by the outer layer of MECs. Because of this, the MEC layer serves as an epithelial “gatekeeper,” by generating boundaries that help organize breast tissue. A recent paper looks at this gatekeeper function of MECs and finds that two proteins, SLIT and ROBO2, are important in regulating the proliferation of MECs. And, in turn, the growth of the MEC layer regulates the branching of mammary tissue. Image above shows mammary tissue in normal (left) or Robo mutant (right) mice. The loss of Robo leads to excessive branching (close-up views of boxed regions on bottom).

Macias, H., Moran, A., Samara, Y., Moreno, M., Compton, J., Harburg, G., Strickland, P., & Hinck, L. (2011). SLIT/ROBO1 Signaling Suppresses Mammary Branching Morphogenesis by Limiting Basal Cell Number Developmental Cell, 20 (6), 827-840 DOI: 10.1016/j.devcel.2011.05.012
Copyright ©2011 Elsevier Ltd. All rights reserved.

June 27, 2011

In my grad school days, I was an asymmetric cell division aficionado. I loved the asymmetric cell division that I studied for those years, the one-cell stage worm embryo. With that statement out of the way, I can admit that I secretly coveted the extremely asymmetric divisions of ooctyes. Check out today’s lovely image of a mouse oocyte, from the cover of Current Biology.

Rather than dividing to produce two identical daughter cells, an oocyte divides to produce a large egg ready for fertilization and a very small polar body. This extreme asymmetric division allows the egg to retain all of the crucial cytoplasm to support a future early embryo. This asymmetry is necessary for fertility and development, but the mechanisms required for this event are not completely understood. A recent paper describes the importance of two novel actin nucleators called Spire1 and Spire2 in mouse meiotic divisions. These Spire proteins drive the assembly of an actin network that acts as a substrate for positioning of the meiotic spindle, and promotes the cytokinetic cleavage furrow that results in polar body extrusion. Image above shows a mouse oocyte undergoing a meiotic division—chromosomes are cyan, microtubules are blue, and cortical actin is red.

BONUS!! Check out this great movie showing spindle positioning in normal (left) and Spire-deficient (right) ooctyes.

To see the cover of Current Biology for this issue, which features the above image, click here.

Pfender, S., Kuznetsov, V., Pleiser, S., Kerkhoff, E., & Schuh, M. (2011). Spire-Type Actin Nucleators Cooperate with Formin-2 to Drive Asymmetric Oocyte Division Current Biology DOI: 10.1016/j.cub.2011.04.029
Copyright ©2011 Elsevier Ltd. All rights reserved.

April 28, 2011

The rods and cones in our retinas detect light. Thankfully, amazing cameras do the same and have captured images of these photoreceptor cells in today’s image.

The outer segments of photoreceptor cells are modified cilia that detect light at the back of the eye. Like the cilia in many other cell types, these outer segments can’t synthesize their own proteins but instead depend on transport of proteins from the cell body along ciliary microtubules. IFT proteins (intraflagellar transport) are important for this transport of material, and a recent paper describes the roles of the IFT20 protein in the retina. IFT20 is required for transport into the outer segments and is uniquely localized to the Golgi complex. Keady and colleagues conclude that IFT20 functions both as part of and independently of the typical IFT system. Images above show retinal sections of mice with normal IFT20 (top) and IFT20 mutated in cone cells (bottom). The lack of RG opsin (green) in IFT20 mutants indicates an absence of cone cells, while normal rhodopsin staining (red) indicates that rod cells are unaffected in mutants.

Keady, B., Le, Y., & Pazour, G. (2011). IFT20 is required for opsin trafficking and photoreceptor outer segment development Molecular Biology of the Cell, 22 (7), 921-930 DOI: 10.1091/mbc.E10-09-0792

March 17, 2011

One of the first jobs an embryo must complete is to orient the body’s head/tail axis. It seems simple enough, but for an early embryo with not many cells, it is an amazing task. A recent paper describes the use of amazing microscopy to visualize this process in a mouse embryo.

The anterior visceral endoderm (AVE) is a subset of cells from the visceral endoderm that sets up the anterior-posterior (head-tail) body axis by migrating to the future anterior region. A recent paper precisely describes AVE migration and the relationship between the AVE and its neighbors. In this paper, Trichas and colleagues show that the AVE cell move by exchanging neighbors, or intercalate, within an unbroken epithelial sheet. In addition, AVE migration is regulated by different localization patterns of actin and certain signaling pathways. Images above are 3D reconstructions of mouse embryo images, with AVE cells labeled green and two different epithelial junction proteins are labeled in magenta (ZO-1 is top, E-cadherin is bottom). Before (left), during (middle), and after (right) migration, the epithelial sheet remains intact due to the cell intercalation of the AVE.

BONUS!! Below is a movie of how 3D renderings compare with the raw images that are acquired on the microscope. For many more awesome movies, check out the link here.

Trichas, G., Joyce, B., Crompton, L., Wilkins, V., Clements, M., Tada, M., Rodriguez, T., & Srinivas, S. (2011). Nodal Dependent Differential Localisation of Dishevelled-2 Demarcates Regions of Differing Cell Behaviour in the Visceral Endoderm PLoS Biology, 9 (2) DOI: 10.1371/journal.pbio.1001019

March 7, 2011

Look all the way down to your toes and you’ll appreciate the feat (pun absolutely intended!) that your neurons accomplish in relaying signals over long distances to your brain. A recent paper discusses the interactions between the first sets of motor and sensory axons that find their way into limbs during development.

During development, motor and sensory axons align together as they project into a developing limb. A group recently showed how motor and sensory axons are mutually dependent on one another for their correct trajectories into a developing limb, and identified an important role for a protein called Neuropilin-1 in these interactions. Image above from the cover of PLoS Biology shows sensory (red) and motor (green) axons in the brachial plexus, a region where motor and sensory axons converge before being sorted into bundles. This tight bundling of the axons is affected in mice that lack Neuropilin-1 in either type of axon.

Huettl, R., Soellner, H., Bianchi, E., Novitch, B., & Huber, A. (2011). Npn-1 Contributes to Axon-Axon Interactions That Differentially Control Sensory and Motor Innervation of the Limb PLoS Biology, 9 (2) DOI: 10.1371/journal.pbio.1001020

Cover of PLoS Biology can be found here.

February 24, 2011

Don’t assume that two identical-looking cells are the same…they may both be rounded and cute, but there is a lot of exciting stuff brewing inside. A recent paper describes the use of a clever microscopy technique to look at how subtle differences in a transcription factor’s kinetics can predict early patterning in the mouse embryo.

There has always been debate and discussion about when the differences that lead to lineage patterning first appear in the cells of very early embryos. Although cells in the very early mouse embryo appear morphologically identical, a recent paper describes the different kinetics of one transcription factor in different cells in the mouse embryo. To measure these differences, Plachta and colleagues tagged the transcription factor Oct4 with a special fluorescent marker that is activated by a certain wavelength of light. Once this marker was activated in certain cells in the 4- and 8-cell embryo, the movement of Oct4 into and out of the nucleus (where it does its job by binding to DNA) was monitored. One group of cells had slower rates of export and import and was more likely to give rise to the inner cell mass, while the second group had higher rates and was more likely to give rise to the extra-embryonic lineage. Image shows an 8-cell embryo with the Oct4 marker activated (green) in the nucleus of one specific cell.

Plachta, N., Bollenbach, T., Pease, S., Fraser, S., & Pantazis, P. (2011). Oct4 kinetics predict cell lineage patterning in the early mammalian embryo Nature Cell Biology, 13 (2), 117-123 DOI: 10.1038/ncb2154
Adapted by permission from Macmillan Publishers Ltd, copyright 2011