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

December 17, 2012

Today’s image is from a paper on the development of the zebrafish eye lens. As I look at the paper’s stunning images, I’m sure that these cute little eyes are following me around my room.

The eye lens is composed of two cell types called lens epithelial cells and lens fibers. During development of the eye, lens fibers are generated from dividing lens epithelial cells, and later undergo morphogenesis. During morphogenesis, these new lens fibers elongate and then migrate toward the midline of lens, with newer lens fibers displacing and compacting older fiber layers as the entire lens grows. A recent paper investigates the relationship between morphogenesis and cell interactions with the underlying extracellular matrix (ECM). Hayes and colleagues found that fibronectin1 (Fn1), an ECM component, and integrin α5, the Fn1 cellular binding partner, are both required for lens fiber morphogenesis in developing zebrafish. Mutations in either gene cause defects in lens fiber adhesion, elongation, and packing, in turn leading to cataracts. Hayes and colleagues suggest that lens fibers migrate along an Fn1-containing substrate, which in turn activates the signaling required for lens fiber morphogenesis. In the images above, Fn1 is labeled in the developing lens of control zebrafish (top) and fn1 mutants (bottom). The control lens shows Fn1 (red) at the apical side of the lens epithelium (asterisks) and in lens fibers at the posterior (arrows), while the mutant shows reduced levels of Fn1.

Hayes, J., Hartsock, A., Clark, B., Napier, H., Link, B., & Gross, J. (2012). Integrin 5/fibronectin1 and focal adhesion kinase are required for lens fiber morphogenesis in zebrafish Molecular Biology of the Cell, 23 (24), 4725-4738 DOI: 10.1091/mbc.E12-09-0672

September 6, 2012

Next time you are cursing your yard for having to prune your bushes, just take a cold sip of lemonade and know that you are helping your shrubs thrive. Or, you are just making them all look like green meatballs, like my shrubs. Win-win! Pruning is an essential part of development, and a recent paper shows pruning of the vasculature in the developing zebrafish brain.

Our brains are surrounded by a complex network of blood vessels that deliver oxygen and nutrients to the neurons. Although the existence of this vasculature has long been appreciated and studied, it has not been clear how the network is formed during development. A recent paper uses confocal live imaging to track the development of the vessel network in the developing zebrafish midbrain. Chen and colleagues found that the zebrafish brain undergoes both blood vessel growth and pruning during development. Blood vessel pruning is driven by blood flow—decreased blood flow triggers pruning, while increased blood flow impairs pruning. In the images above, a segment of blood vessel from the midbrain vasculature undergoes pruning (red arrow).

Chen Q, Jiang L, Li C, Hu D, Bu JW, Cai D, & Du JL (2012). Haemodynamics-driven developmental pruning of brain vasculature in zebrafish. PLoS biology, 10 (8) PMID: 22904685

August 16, 2012

One of the most fascinating and terrifying things about human health is how a single mutation in a single gene can cause such dramatic disorders and diseases. A person may have a lifetime of adjustments that their disorder or handicap requires, a constant looking-over-your-shoulder for that increased cancer risk (BRCA, I’m looking at you), or far worse. One mutation can affect one small part of a cell that, in no small way, affects everything. Today’s image is from a paper on primary cilia, and discusses applications of the research into understanding human ciliopathies.

Cilia are microtubule-based protrusions that function in sweeping material across a tissue (motile cilia) or as sensory orgnanelles (primary cilia). The link between several disorders and ciliary defects has driven more research towards understanding how cilia are formed and how they function. Specifically, certain disorders that cause blindness result from defective or dying photoreceptor cells in the retina, which have the largest primary cilia found in mammals—rod and cone photoreceptors. In a recent paper, Zhang and colleagues identified the roles of a novel protein, Ttc26, in ciliogenesis. Zebrafish with reduced levels of Ttc26 had ciliary defects both in kidneys and photoreceptor cells. Without Ttc26, cells produced cilia that were short and defective. In the images above of rat photoreceptor cells (green), Ttc26 (red) is seen in the transition zone of cilia. Zhang and colleagues suggest that based on the importance of Ttc26 in ciliogenesis, patients with ciliary disorders should be screened for ttc26 gene mutations.

Zhang Q, Liu Q, Austin C, Drummond I, & Pierce EA (2012). Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Molecular biology of the cell, 23 (16), 3069-78 PMID: 22718903

May 17, 2012

Hit the road, Jack! Cells undergo cell death all the time, but it’s important for a tissue to clear these cells out before problems crop up. Today’s image is from a paper showing the migration of apoptotic cells, and revealing the role a protein called elmo1 in cell corpse clearing.

Apoptosis is programmed cell death, and is as part of normal development and tissue function as cell division is. Apoptotic cells must be cleared out of the healthy tissue, and failure to do so can result in inflammation and autoimmunity. A recent paper describes the clearance of apoptotic cells in the developing brain of zebrafish, using real-time microscopy to track apoptotic cells. van Ham and colleagues found that apoptotic cells are able to migrate to the periphery of the tissue to contribute to their own removal, and use their own actin cytoskeleton to do so. Later in development, cell corpses are engulfed by large macrophage cells with the help of a protein called elmo1, a protein known to play a role in cell engulfment in other tissues. In the images above, a cell in the process of undergoing apoptosis migrates through the neural tube of a zebrafish embryo.

van Ham, T., Kokel, D., & Peterson, R. (2012). Apoptotic Cells Are Cleared by Directional Migration and elmo1- Dependent Macrophage Engulfment Current Biology, 22 (9), 830-836 DOI: 10.1016/j.cub.2012.03.027
Copyright ©2012 Elsevier Ltd. All rights reserved.

May 3, 2012

Where did you come from? Understanding the answer to this question helps you get a grasp on who you are currently, and who you are becoming. Whoa, that was deep…enough of that crap! A recent paper puts the psychotherapy treatment on cells in the developing heart and adds to our understanding of where they are from.

The change that takes place in a developing heart is astounding—a simple tube structure with a single layer of cardiac muscle cells called cardiomyocytes must develop into a complex adult structure. How the early cardiomyocytes divide and move around to form the adult heart is difficult to map out due to their dynamic behavior and their location in a tissue that is difficult to image. A recent paper describes the use of a recently-developed technology called Brainbow, in which different cells can be labeled with about 90 different colors. Using Brainbow techniques, Gupta and Poss were able to track the division and movement of individual cardiomyocytes in the developing zebrafish heart, and found that the cells expand the cardiac tissue in patches of various sizes and shapes. By using clonal dominance as a mechanism for tissue expansion, the process is reminiscent of stem cells. The image above shows the surface of the ventricular side of a developing heart, each color representing a different clonal patch that arose from a single cardiomyocyte.

Gupta, V.; Poss, K. (2012). Clonally dominant cardiomyocytes direct heart morphogenesis Nature, 484 (7395), 479-484 DOI: 10.1038/nature11045

Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

 

September 5, 2011

When you hear the word “angiogenesis,” do you start hissing? Many of us associate angiogenesis with tumors on their way to becoming malignant cancer. Well, if it weren’t for angiogenesis, we’d all be in trouble. Angiogenesis is the formation of blood vessels from pre-existing ones, and is a key process during development.

Blood vessels are the tubular structures that transport all of the good stuff in our blood. The formation of blood vessels depends on angiogenesis, the process in which vessels are created from pre-existing ones. Angiogenesis is a tightly regulated process, as the blood vessels in many organs have a stereotypic organization, abundance, and shape. For example, zebrafish embryos have a regular pattern of blood vessels sprouting from the aorta, along the trunk of the fish. A recent paper describes the importance of Semaphorin-PlexinD1 signaling in the organization of these blood vessels. According to Zygmunt and colleagues, Semaphorin-PlexinD1 signaling ensures the correct spatial distribution and number of blood vessels along the embryo’s trunk. Without correct Semaphorin-PlexinD1 signaling, too many vessels sprout along the aorta, as seen in the images above. Normal embryos (left) have a very regular pattern of blood vessels (green, "SeA") sprouting up, while embryos lacking Semaphorin-PlexinD1 signaling (right) have too many sprouts, with incorrect positioning.

Zygmunt, T., Gay, C., Blondelle, J., Singh, M., Flaherty, K., Means, P., Herwig, L., Krudewig, A., Belting, H., Affolter, M., Epstein, J., & Torres-Vázquez, J. (2011). Semaphorin-PlexinD1 Signaling Limits Angiogenic Potential via the VEGF Decoy Receptor sFlt1 Developmental Cell DOI: 10.1016/j.devcel.2011.06.033
Copyright ©2011 Elsevier Ltd. All rights reserved.

June 6, 2011

The human body is amazing, but cannot hold a candle to many organisms when it comes to limb regeneration. Zebrafish are able to regenerate amputated fins, including the sensory axons in the fin that sense touch. Today’s image is from a paper discussing the signals required for this process.

When tissue is regenerated, there are several different cell types that must be involved in order to heal the entire tissue. A recent paper looks at the regeneration of skin cells and sensory neuron axons in zebrafish to determine how the process of wound healing requires the coordination of several cell types. Zebrafish larvae can regenerate both the skin tissue and sensory axons of an amputated tail fin, and Rieger and Sagasti found that the reactive oxygen species hydrogen peroxide (H2O2) plays an important role in this coordination. Injured skin cells release the H2O2 signal, and this signal then promotes robust regeneration of the sensory axons. Images above show the sensory axons in uninjured (top) and amputated (bottom) tail fins over time. Axons were regenerated into the amputated region (dotted line, shaded region), as seen as the red trajectories of axon tips (left-most image).

Rieger, S., & Sagasti, A. (2011). Hydrogen Peroxide Promotes Injury-Induced Peripheral Sensory Axon Regeneration in the Zebrafish Skin PLoS Biology, 9 (5) DOI: 10.1371/journal.pbio.1000621

December 20, 2010

We know so much information about cells by the amazing researchers that study how cells function in culture. It is always refreshing to see some biologists take this knowledge into a three-dimensional organism to help us understand even more about cells and development. It is even better when we get to see the images!

During development of an organism, cells frequently have to migrate from the spot where they were born to the spot where they will eventually form tissue and organs. Migration is a complicated process, and a recent paper describes the importance of the interaction between the plasma membrane and the cytoskeletal network directly underneath in order for migration to happen smoothly. The images above show three different types of membrane protrusions (blebs, filopodia, and lamellapodia) seen in prechordal plate progenitor cells in zebrafish embryos as they migrate to their eventual destination.

BONUS!! Check out a cool movie of the cell migration here.

Diz-Muñoz, A., Krieg, M., Bergert, M., Ibarlucea-Benitez, I., Muller, D., Paluch, E., & Heisenberg, C. (2010). Control of Directed Cell Migration In Vivo by Membrane-to-Cortex Attachment PLoS Biology, 8 (11) DOI: 10.1371/journal.pbio.1000544