November 12, 2014

You might think that the “kiss-and-hop” is a dance move strictly forbidden at a Duggar homeschool prom, but it refers to the quick dynamics of the microtubule-associated protein tau. Today’s image is from a paper describing unexpected results about how tau resides on and regulate microtubules without physically impeding microtubule motors. 

The microtubule-associate protein tau binds to and stabilizes the microtubules within an axon. As most tau is believed to decorate axonal microtubules, it was previously unclear how tau can function in its non-microtubule-dependent roles, or how the presence of tau does not interfere with microtubule motors and axonal transport. A recent paper by Janning and colleagues describes the use of single-molecule tracking of tau in living cells. Janning and colleagues found that tau resides on a single microtubule for 40ms before hopping to the next microtubule, and that this unexpectedly short residence time is sufficient to affect microtubule stability. This “kiss-and-hop” mechanism allows for normal axonal transport, and suggests how some tau functions away from microtubules. In the images above, tau (red) is labeled in mouse cortical neurons, as are microtubules (green) and the nucleus (blue).  

Janning, D., Igaev, M., Sundermann, F., Bruhmann, J., Beutel, O., Heinisch, J., Bakota, L., Piehler, J., Junge, W., & Brandt, R. (2014). Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons Molecular Biology of the Cell, 25 (22), 3541-3551 DOI: 10.1091/mbc.E14-06-1099

October 17, 2014

For years, the prettiest cells to image were flat cells in a dish. Thanks to the tireless work of many, beautiful high-resolution images can now come from tissue within a living organism. Today’s image is from a paper showing improved techniques for imaging fine cellular processes within large volumes, from the lab of recent Nobel prize winner, Eric Betzig. 

A material’s refractive index refers to how light travels through it; the simplest example being how light bends when passed through water. The refractive index heterogeneities stemming from the many cell types, morphologies, and subdomains within a living organism are a challenge to microscopists. As described in a paper from earlier this year, Wang and colleagues improved on previous techniques for imaging within large volumes. Wang and colleagues use adaptive optics (AO), which corrects for the microscope’s aberrations that limit image resolution, in a mode fast enough to correct for the various aberrations within a large sample, without inducing photodamage or photobleaching. The image above shows a 3D rendering from deep within a living zebrafish brain, with oligodendrocytes (magenta) and neuronal nuclei (green) visible.

Wang, K., Milkie, D., Saxena, A., Engerer, P., Misgeld, T., Bronner, M., Mumm, J., & Betzig, E. (2014). Rapid adaptive optical recovery of optimal resolution over large volumes Nature Methods, 11 (6), 625-628 DOI: 10.1038/nmeth.2925
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

September 11, 2014

As your therapist likely tells you, understanding where you came from is key to accepting where you are now. Take that therapist’s task and multiply it by several million—you now understand the tough job ahead of developmental biologists trying to track cell lineages in complex organisms. Today’s colorful image is from a paper describing a new computational framework for reconstructing cell lineages. 

The successful tracking of cell position, division, and movement in a developing organism has been a goal for countless developmental biologists. Reconstructing cell lineages in organisms like fruit flies and mice, however, is difficult due to the complexity of cell organization and behavior, poor image quality of thick embryos, the enormous size of the data sets, and an uncompromising need for accuracy. A recent paper by Amat and colleagues describes the development and use of a new open-source framework that reconstructs cell lineages with high accuracy and speed. Their system uses four dimensional and terabyte-sized image data sets of nuclei-tracked embryos, imaged using three different types of fluorescence microscopy. The images above show the first reconstruction of early fruit fly nervous system development (S1 neuroblasts), with precursor cell tracks color-coded for time (purple to yellow).

Amat, F., Lemon, W., Mossing, D., McDole, K., Wan, Y., Branson, K., Myers, E., & Keller, P. (2014). Fast, accurate reconstruction of cell lineages from large-scale fluorescence microscopy data Nature Methods, 11 (9), 951-958 DOI: 10.1038/nmeth.3036
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

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 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

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

July 17, 2013

We don’t need to reinvent the wheel (even if someone tried to in 2001...click here).  We use the wheel for so many things ranging from transport to energy.  Cells have proven clever at co-opting machinery for multiple processes, as the paper from today’s image describes.  This recent paper shows the use of specific machinery in both cytokinesis and neuronal migration.

When neurons migrate, there is a leading process in the front of the cell body and a trailing process.  The leading process contains actin filaments that enable the cell body of the neuron to move forward.  A recent paper describes how the microtubule-based motor kinesin-6 plays an important role in neuronal migration.  Kinesin-6 is best known for its role in cytokinesis, the physical division of a cell after mitosis.  Falnikar and colleagues found that kinesin-6 concentrates in the same region as actin filaments in the leading process of a migrating neuron.  Without kinesin-6, neurons lose their bipolar leading-trailing process morphology, concentrate actin filaments in more than one process, and either remain stationary or continually change the direction of migration.  In addition, Falnikar and colleagues found that kinesin-6 signals through the GTPase activating protein MgcRacGAP to regulate the actin cytoskeleton, as it does during cytokinesis.  In the images above, control neurons (top time-lapse series) moved in a single direction, while neurons depleted of kinesin-6 bottom) frequently changed directions.

BONUS!!  Check out a movie of a wandering, migrating kinesin-6-depleted neuron below.

Aditi Falnikar, Shubha Tole, Mei Liu, Judy S. Liu, & Peter W. Baas (2013). Polarity in Migrating Neurons Is Related to a Mechanism Analogous to Cytokinesis Current Biology, 23 (13), 1215-1220 DOI: 10.1016/j.cub.2013.05.027 Copyright ©2013 Elsevier Ltd. All rights reserved.

July 2, 2013

 
Timing is everything….from the fluke encounter in a romantic comedy, to your rush to make the bus/train/plane this morning, to the development of an organism. Today’s image is from a paper describing the temporal patterning involved in the development of the fruit fly optic lobe.

In the fruit fly optic lobe, the medulla processes visual information using 40,000 neurons of over 70 different cell types. The medulla develops from a crescent-shaped tissue from which the neuronal progenitors divide, requiring several different transcription factors. A recent paper describes the sequential patterning of five transcription factors as the medulla neuroblasts age. Li and colleagues found that this temporal patterning of transcription factors is necessary for the diversity of cell types found in the medulla. The images of the developing medulla above show the sequential expression of these five transcription factors—Homothorax (Hth), Eyeless (Ey), Sloppy paired 1 and 2 (Slp), Dichaete (D), and Tailless (Tll)—in five consecutive stripes. Hth is found in the youngest neuroblasts. Ey, Slp, and D are required for turning on the next transcription factor in the cascade. Slp and D are also required for turning off the preceding transcription factor.

Li X, Erclik T, Bertet C, Chen Z, Voutev R, Venkatesh S, Morante J, Celik A, & Desplan C (2013). Temporal patterning of Drosophila medulla neuroblasts controls neural fates. Nature, 498 (7455), 456-62 PMID: 23783517 
Adapted by permission from Macmillan Publishers Ltd, copyright ©2013

June 4, 2013

HighMag is back from an early summer vacation at the beach, and ready to get our microscopic groove on.  Happy Summer, everyone!

Our world is the same size it’s always been, but so many advances in technology have made the world seem a lot smaller.  We can call our brother across the country and video chat with our sister on the other side of the world, all while searching the internet for the lyrics to Snow’s “Informer” (side note…knowing the lyrics won’t help you understand the song AT ALL).  Similarly, a neuron’s axons make the nervous system seem a lot smaller too, with their amazing ability to grow very long.  Today’s image is from a paper showing how microtubule sliding is involved.

Neurons can transmit signals to far away neurons, thanks to the ability of their axons to grow insanely long.  Both actin filaments and microtubules participate in axon growth, with microtubules pushing the growing axon out and actin filaments working directly at the tip of the growing axon, called the growth cone.  A recent paper shows the role of microtubule sliding in the initial growth of neurites in fruit fly neurons.  Lu and colleagues found that the microtubule motor kinesin-1 drives the sliding of microtubules past one other in order to push out the neuron’s growing projection.  This mechanism does not require actin filaments, and is suppressed during maturation of neurons.  In the images above, microtubules (green) can be seen pushing against the tip of a growing neurite in a young neuron (membrane of neuron in red and bottom right series).  The whole neuron is on the left, and the neurite in the boxed region is shown in the time-lapse images on the right.

Lu, W., Fox, P., Lakonishok, M., Davidson, M., & Gelfand, V. (2013). Initial Neurite Outgrowth in Drosophila Neurons Is Driven by Kinesin-Powered Microtubule Sliding Current Biology, 23 (11), 1018-1023 DOI: 10.1016/j.cub.2013.04.050 
Copyright ©2013 Elsevier Ltd. All rights reserved.

May 21, 2013

“LET THERE BE LIGHT!” said the microscopist.  Light plays a crucial role in microscopy and cell biology, and a recent paper describes the use of light to understand protein secretion.

Light is used in microscopy in countless ways—to illuminate a sample, excite a fluorophore, and signal the localization or dynamics of a protein.  Light can also be used to manipulate cellular events through the use of “caged” compounds that become active after illumination by certain wavelengths of light.  This technology gives biologists the ability to spatially and temporally control cellular events in order to understand them better.  Recent advances in this technology use illumination of plant photoreceptors to control protein-protein interactions, but some cellular processes such as protein secretion have been difficult to manipulate.  A recent paper describes the use of the plant photoreceptor UVR8 in the first light-triggered protein secretion system developed.  Chen and colleagues have shown that the recently described UVR8 can conditionally sequester proteins bound for secretion in the ER, and then upon illumination with UV light releases these proteins to the plasma membrane.  In the images above, a neuron before (left) and after (right) UV illumination with this UVR8 system shows the movement of proteins known to be secreted from the soma and dendritic processes (arrowheads), where the ER is distributed, and into the Golgi (arrow), a necessary step in protein secretion.

Chen, D., Gibson, E., & Kennedy, M. (2013). A light-triggered protein secretion system originally published in the Journal of Cell Biology, 201 (4), 631-640 DOI: 10.1083/jcb.201210119

April 29, 2013

There are many, many things in cell biology that can serve as models for fine art, but fewer are more stunning to me than a Purkinje neuron.  Purkinje neurons are some of the largest neurons in the brain, where they participate in motor control from the cerebellum.  Today’s image is from a paper describing what happens when a protein called rictor is depleted from Purkinje neurons.

The two multi-protein complexes mTORC1 and mTORC2 share sensitivity to inhibition by the immunosuppressive drug rapamycin, yet likely have distinct roles in cell function and development.  Each complex is composed of a distinct set of subunits—mTORC1 depends on the protein raptor, while mTORC2 depends on the protein rictor.  A recent paper describes an important role for mTORC2 in neuron size, morphology, and function.  Thomanetz and colleagues found that two different mouse lines lacking the mTORC2 protein rictor had smaller neurons with disrupted function, likely mediated through regulation of PKC (protein kinase C) isoforms.   mTORC1 activity was unaffected in these mutants.  When rictor was depleted from the entire central nervous system, motor function of the mice was affected.  When rictor was depleted from only Purkinje neurons, the cell type with the highest rictor expression, neurons were smaller and their morphology was abnormal.  In the images above, control Purkinje neurons (top) had only one primary dendrite compared with neurons lacking rictor (bottom), which had multiple primary dendrites (notated in different colors, right).  

Thomanetz, V., Angliker, N., Cloetta, D., Lustenberger, R., Schweighauser, M., Oliveri, F., Suzuki, N., & Ruegg, M. (2013). Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size and neuron morphology originally published in the Journal of Cell Biology, 201 (2), 293-308 DOI: 10.1083/jcb.201205030

March 26, 2013

When Outkast sang that “I like the way you mooove,” I immediately figured they were talking my dancing skills.  Turns out, they were really singing about motile cells…true story*.  Today’s image is from a paper showing a link between the chemical signals that tell a cell to move and how the cell actually moves.

As an axon searches for its synaptic target, it sends out a motile extension called a growth cone.  The chemical cues that initiate mobility in the growth cone trigger major cytoskeletal rearrangements at the leading edge, specifically actin filament polymerization and an engagement with the underlying extracellular substrate.  A recent paper describes the signaling that links the chemical cues to the generation of traction forces that move the growth cone forward.  Toriyama and colleagues show that the protein shootin1 is phosphorylated following signaling from the chemoattractant netrin1.  Phosphorylated shootin1, then, triggers actin-extracellular substrate coupling and generates the forces for axonal outgrowth.  In the images above, phosphorylated shootin1 (green) is enriched at filopodial and lamellipodial extensions in growth cones (actin filaments are in red).

*not really

Toriyama, M., Kozawa, S., Sakumura, Y., & Inagaki, N. (2013). Conversion of a Signal into Forces for Axon Outgrowth through Pak1-Mediated Shootin1 Phosphorylation Current Biology, 23 (6), 529-534 DOI: 10.1016/j.cub.2013.02.017 
Copyright ©2013 Elsevier Ltd. All rights reserved. 

January 25, 2013

Neuromuscular junctions (NMJs) are considered by many to be the business end of our nervous system. NMJs connect nerves with muscle cells, stimulating the muscle contractions that allow you to run from the bear that you just spotted glaring at you with a fork and knife in his paws. A recent paper adds to our understanding of the signaling on both sides of the NMJ. 

The two sides of a NMJ, the presynaptic and postsynaptic structures, are highly coordinated for proper development and plasticity of the junction. As with many cell and developmental processes, this coordination relies on the Wnt signaling pathway. In fruit flies, Wnt/Wingless (Wg) functions both pre- and post-synaptically in larval muscle fibers, and results from a recent paper show how this bidirectional signaling is balanced and regulated. Kamimura and colleagues found that the gene trol, which encodes the protein perlecan (a secreted heparan sulfate proteoglycan, for those down with HSPGs), regulates Wg signaling in fruit fly NMJs. trol mutations causes postsynaptic defects and an overproduction of synaptic boutons, which are button-like presynaptic hotspots of neurotransmitter-containing vesicles. In the images above, normal (top) and trol mutant larval NMJs show immunostaining for a presynaptic marker (magenta) and a postsynaptic marker (green). In mutants, some synaptic boutons lack a postsynaptic structure nearby (“ghost boutons", arrowheads) while some NMJs showed an overproduction of small synaptic boutons (“satellite boutons”, arrow).

Kamimura, K., Ueno, K., Nakagawa, J., Hamada, R., Saitoe, M., & Maeda, N. (2013). Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction originally published in the Journal of Cell Biology, 200 (2), 219-233 DOI: 10.1083/jcb.201207036

December 10, 2012

A cell is nothing if not thorough. A cell can regulate a function with one method, but usually employs several methods of regulation to get a job done, ensure that it gets done correctly, and has a backup plan if it goes awry. Today’s image is from a paper describing regulation of a protein by localized levels of mRNA.

For some types of cells, notably polarized cells, the localization of a protein can be regulated through mRNAs. mRNAs are transcribed from DNA, and then later translated into the proteins that function throughout the cell. By transporting mRNAs to specific regions, the cell in turn can have localized levels of proteins. A recent paper shows the specific localization of an mRNA encoding the signaling molecule MKK7 to neuronal growth cones, which are dynamic extension of a developing axon searching for its final target. According to Feltrin and colleagues, this localization of MKK7 mRNA may result in localized levels of MKK7 protein. MKK7 mRNA localization modulates JNK signaling, which in turn regulates microtubule bundling during neuronal outgrowth. In the images above, cells with reduced levels of MKK7 mRNA (bottom) have curled and bent microtubules (red in merged, black in right panels), compared to control cells (top).

Daniel Feltrin, Ludovico Fusco, Harald Witte, Francesca Moretti, Katrin Martin, Michel Letzelter, Erika Fluri, Peter Scheiffele, & Olivier Pertz (2012). Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation PLOS Bio, 10 (12) : 10.1371/journal.pbio.1001439

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

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 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. 

October 19, 2012

The next time you see a fruit fly buzzing around your kitchen, take a beat before you smack it with a swatter and remind yourself of the amazing discoveries due to organisms like the (not so) lowly fruit fly. Maybe you’ll offer a thank-you glass of grape juice instead and show the intruder back outside. Today’s image is from a paper describing a fly model of a serious human disease, and serves as a great example of the power in a model organism.

Spinal muscular atrophy (SMA) is a heritable disease that results in infant mortality due motor neuron dysfunction and rapid degeneration of muscle. SMA is caused by the depletion of the SMN (survival motor neuron) protein. A recent paper describes the use of fruit flies in studying SMA, and shows that flies lacking SMN have reduced muscle size and defective motor neuron neurotransmission similar to SMA patients. Imlach and colleagues found that replenishing SMN levels in motor neurons and muscles did not reverse the defects of SMN depletion, yet increasing SMN levels in partner cells (proprioceptive neurons and interneurons) can reverse the defects. These results suggest that SMN depletion primarily affects the sensory-motor network, with secondary effects seen in the motor circuit. In addition, Imlach and colleagues found that increasing motor neural circuit excitability, either genetically or with drugs, could relieve SMN-depletion defects. Using this fly model of SMA, these results suggest that SMA patients may improve by enhancing motor neural network activity. The images above show the differences in muscle size in wild-type (left) and SMN-depleted (right) flies.

Imlach WL, Beck ES, Choi BJ, Lotti F, Pellizzoni L, & McCabe BD (2012). SMN Is Required for Sensory-Motor Circuit Function in Drosophila. Cell, 151 (2), 427-39 PMID: 23063130
Copyright ©2012 Elsevier Ltd. All rights reserved.

 

September 18, 2012

It’s hard to not get excited about stem cells and their potential. The advances that will likely take place due to stem cells (and already have!) couldn’t have been dreamed up by even George Jetson’s creators. (Side note: where’s my flying car and robot housekeeper?!) Today’s image is from a paper showing the success of stem cells in healing a spinal cord injury.

Stem cells are unspecialized cells able to differentiate into various other cell types throughout development and adulthood. The prospect of using stem cells in treating diseases or repairing traumatic injuries drives the research of many biologists. A recent paper describes how stem cells can repair a spinal cord injury in mice. Lu and colleagues grafted mouse neural stem cells onto the sites of severe spinal cord injuries, and found that these cells differentiated into different cell types, including neurons. These neurons projected long axons that were able to form synapses with host neurons, and allowed functional recovery of the spinal cord. Human stem cells exhibited similar growth within the injured spinal cords of mice. The images above show the site of an injured spinal cord, several weeks after the injury. Neural stem cells (green) were able to grow and completely fill in the injured area.

Copyright ©2012 Elsevier Ltd. All rights reserved.
Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, & Tuszynski MH (2012). Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell, 150 (6), 1264-73 PMID: 22980985