What looks a little like distant planets with some mysterious surface features are actually assemblies of proteins normally found in the cell's nucleolus, a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from differences in how the proteins in each compartment mix with water and with each other. These differences let the proteins readily separate from each other into the three nucleolus compartments.

This photo of nucleolus proteins in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows each of the nucleolus compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue). The researchers have found that these compartments spontaneously fuse with each other on encounter without mixing with the other compartments.

For more details on this research, see this press release from Princeton. Related to video 3789, video 3791 and image 3792.

Along with blood vessels (red) and nerve cells (green), this mouse brain shows abnormal protein clumps known as plaques (blue). These plaques multiply in the brains of people with Alzheimer's disease and are associated with the memory impairment characteristic of the disease. Because mice have genomes nearly identical to our own, they are used to study both the genetic and environmental factors that trigger Alzheimer's disease. Experimental treatments are also tested in mice to identify the best potential therapies for human patients.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

Pigment cells are cells that give skin its color. In fishes and amphibians, like frogs and salamanders, pigment cells are responsible for the characteristic skin patterns that help these organisms to blend into their surroundings or attract mates. The pigment cells are derived from neural crest cells, which are cells originating from the neural tube in the early embryo. This image shows neural crest cell-derived, migrating pigment cells in a salamander. Investigating pigment cell formation and migration in animals helps answer important fundamental questions about the factors that control pigmentation in the skin of animals, including humans. Related to images 5754, 5755, 5756 and 5757.

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Stained cell membranes (green) and cell walls (red) reveal the connections between cells. Younger cells take up more cell membrane stain, while older cells take up more cell wall stain, leading to the color differences seen here. This image was captured using spinning disk confocal microscopy.

Related to images 6970 and 6971.

A section of mouse colon with gut bacteria (center, in green) residing within a protective pocket. Understanding how microorganisms colonize the gut could help devise ways to correct for abnormal changes in bacterial communities that are associated with disorders like inflammatory bowel disease.

A genetic disorder of the nervous system, neurofibromatosis causes tumors to form on nerves throughout the body, including a type of tumor called an optic nerve glioma that can result in childhood blindness. The image was used to demonstrate the unique imaging capabilities of one of our newest (at the time) laser scanning microscopes and is of a wildtype (normal) mouse retina in the optic fiber layer. This layer is responsible for relaying information from the retina to the brain and was fluorescently stained to reveal the distribution of glial cells (green), DNA and RNA in the cell bodies of the retinal ganglion neurons (orange) and their optic nerve fibers (red), and actin in endothelial cells surrounding a prominent branching blood vessel (blue). By studying the microscopic structure of normal and diseased retina and optic nerves, we hope to better understand the altered biology of the tissues in these tumors with the prospects of developing therapeutic interventions.

Bacteria engineered to act as genetic clocks flash in synchrony. Here, a "supernova" burst in a colony of coupled genetic clocks just after reaching critical cell density. Superimposed: A diagram from the notebook of Christiaan Huygens, who first characterized synchronized oscillators in the 17th century.

A protein called tubulin (green) accumulates in the center of a nucleus (outlined in pink) from an aging cell. Normally, this protein is kept out of the nucleus with the help of gatekeepers known as nuclear pore complexes. But NIGMS-funded researchers found that wear and tear to long-lived components of the complexes eventually lowers the gatekeepers' guard. As a result, cytoplasmic proteins like tubulin gain entry to the nucleus while proteins normally confined to the nucleus seep out. The work suggests that finding ways to stop the leakage could slow the cellular aging process and possibly lead to new therapies for age-related diseases.

A fruit fly (Drosophila melanogaster) egg chamber with microtubules shown in green and actin filaments shown in red. Egg chambers are multicellular structures in fruit flies ovaries that each give rise to a single egg. Microtubules and actin filaments give the chambers structure and shape. This image was captured using a confocal microscope.

More information on the research that produced this image can be found in the Current Biology paper "Gatekeeper function for Short stop at the ring canals of the Drosophila ovary" by Lu et al.

Cell-like compartments that spontaneously emerged from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Image created using confocal microscopy.

For more photos of cell-like compartments from frog eggs view: 6584, 6585, 6586, 6591, 6592.

For videos of cell-like compartments from frog eggs view: 6587, 6588, 6589, and 6590.

This image results from a research project to visualize which regions of the adult fruit fly (Drosophila) brain derive from each neural stem cell. First, researchers collected several thousand fruit fly larvae and fluorescently stained a random stem cell in the brain of each. The idea was to create a population of larvae in which each of the 100 or so neural stem cells was labeled at least once. When the larvae grew to adults, the researchers examined the flies’ brains using confocal microscopy. With this technique, the part of a fly’s brain that derived from a single, labeled stem cell “lights up. The scientists photographed each brain and digitally colorized its lit-up area. By combining thousands of such photos, they created a three-dimensional, color-coded map that shows which part of the Drosophila brain comes from each of its ~100 neural stem cells. In other words, each colored region shows which neurons are the progeny or “clones” of a single stem cell. This work established a hierarchical structure as well as nomenclature for the neurons in the Drosophila brain. Further research will relate functions to structures of the brain.

Related to image 5868 and video 5843

Like a paint-by-numbers picture, painted probes tint individual human chromosomes by targeting specific DNA sequences. Chromosome 13 is colored green, chromosome 14 is in red and chromosome 15 is painted yellow. The image shows two examples of fused chromosomes—a pair of chromosomes 15 connected head-to-head (yellow dumbbell-shaped structure) and linked chromosomes 13 and 14 (green and red dumbbell). These fused chromosomes—called dicentric chromosomes—may cause fertility problems or other difficulties in people.

The human skin cells pictured contain genetic modifications that make them pluripotent, essentially equivalent to embryonic stem cells. A scientific team from the University of Wisconsin-Madison including researchers Junying Yu, James Thomson, and their colleagues produced the transformation by introducing a set of four genes into human fibroblasts, skin cells that are easy to obtain and grow in culture.

Here, a human HeLa cell (a type of immortal cell line used in laboratory experiments) is undergoing cell division. They come from cervical cancer cells that were obtained in 1951 from Henrietta Lacks, a patient at the Johns Hopkins Hospital. The final stage of division, called cytokinesis, occurs after the genomes—shown in yellow—have split into two new daughter cells. The myosin II is a motor protein shown in blue, and the actin filaments, which are types of protein that support cell structure, are shown in red.

This video results from a research project to visualize which regions of the adult fruit fly (Drosophila) brain derive from each neural stem cell. First, researchers collected several thousand fruit fly larvae and fluorescently stained a random stem cell in the brain of each. The idea was to create a population of larvae in which each of the 100 or so neural stem cells was labeled at least once. When the larvae grew to adults, the researchers examined the flies’ brains using confocal microscopy. With this technique, the part of a fly’s brain that derived from a single, labeled stem cell “lights up.” The scientists photographed each brain and digitally colorized its lit-up area. By combining thousands of such photos, they created a three-dimensional, color-coded map that shows which part of the Drosophila brain comes from each of its ~100 neural stem cells. In other words, each colored region shows which neurons are the progeny or “clones” of a single stem cell. This work established a hierarchical structure as well as nomenclature for the neurons in the Drosophila brain. Further research will relate functions to structures of the brain.

Related to images 5838 and 5868.

Hydra magnipapillata is an invertebrate animal used as a model organism to study developmental questions, for example the formation of the body axis.

Cell-like compartments that spontaneously emerged from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Video created using confocal microscopy.

For more photos of cell-like compartments from frog eggs view: 6584, 6585, 6586, 6591, 6592, and 6593.

For videos of cell-like compartments from frog eggs view: 6587, 6588, 6589.

The three neurons (red) visible in this image were derived from human embryonic stem cells. Undifferentiated stem cells are green here. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Actin is an essential protein in a cell's skeleton (cytoskeleton). It forms a dense network of thin filaments in the cell. Here, researchers have used a technique called stochastic optical reconstruction microscopy (STORM) to visualize the actin network in a cell in three dimensions. The actin strands were labeled with a dye called Alexa Fluor 647-phalloidin.  This image appears in a study published by Nature Methods, which reports how researchers use STORM to visualize the cytoskeleton.

Wound healing requires the action of stem cells. In mice that lack the Sept2/ARTS gene, stem cells involved in wound healing live longer and wounds heal faster and more thoroughly than in normal mice. This confocal microscopy image from a mouse lacking the Sept2/ARTS gene shows a tail wound in the process of healing. See more information in the article in Science.

Related to images 3497 and 3500.

A 20-µm thick section of mouse midbrain. The nerve cells are transparent and weren’t stained. Instead, the color is generated by interaction of white polarized light with the molecules in the cells and indicates their orientation.

The image was obtained with a polychromatic polarizing microscope that shows the polychromatic birefringent image with hue corresponding to the slow axis orientation. More information about the microscopy that produced this image can be found in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak.

This image of the human brain uses colors and shapes to show neurological differences between two people. The blurred front portion of the brain, associated with complex thought, varies most between the individuals. The blue ovals mark areas of basic function that vary relatively little. Visualizations like this one are part of a project to map complex and dynamic information about the human brain, including genes, enzymes, disease states, and anatomy. The brain maps represent collaborations between neuroscientists and experts in math, statistics, computer science, bioinformatics, imaging, and nanotechnology.

This image captures the spiral-shaped ovary of an anglerfish in cross-section. Once matured, these eggs will be released in a gelatinous, floating mass. For some species of anglerfish, this egg mass can be up to 3 feet long and include nearly 200,000 eggs.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

A Trigonium diatom imaged by a quantitative orientation-independent differential interference contrast (OI-DIC) microscope. Diatoms are single-celled photosynthetic algae with mineralized cell walls that contain silica and provide protection and support. These organisms form an important part of the plankton at the base of the marine and freshwater food chains. The width of this image is 90 μm.

More information about the microscopy that produced this image can be found in the Journal of Microscopy paper “An Orientation-Independent DIC Microscope Allows High Resolution Imaging of Epithelial Cell Migration and Wound Healing in a Cnidarian Model” by Malamy and Shribak.

Composite image of beta-galactosidase showing how cryo-EM’s resolution has improved dramatically in recent years. Older images to the left, more recent to the right. Related to image 5882. NIH Director Francis Collins featured this on his blog on January 14, 2016.

The lubber grasshopper, found throughout the southern United States, is frequently used in biology classes to teach students about the respiratory system of insects. Unlike mammals, which have red blood cells that carry oxygen throughout the body, insects have breathing tubes that carry air through their exoskeleton directly to where it's needed. This image shows the breathing tubes embedded in the weblike sheath cells that cover developing egg chambers.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

Speckle microscopy analysis of actin cytoskeleton force. This is an example of NIH-supported research on single-cell analysis. Images in related series; Related to 2799, 2800, 2801, 2802 and 2803.

The photo shows a confocal microscopy image of perineuronal nets (PNNs), which are specialized extracellular matrix (ECM) structures in the brain. The PNN surrounds some nerve cells in brain regions including the cortex, hippocampus and thalamus. Researchers study the PNN to investigate their involvement stabilizing the extracellular environment and forming nets around nerve cells and synapses in the brain. Abnormalities in the PNNs have been linked to a variety of disorders, including epilepsy and schizophrenia, and they limit a process called neural plasticity in which new nerve connections are formed. To visualize the PNNs, researchers labeled them with Wisteria floribunda agglutinin (WFA)-fluorescein. Related to image 3741.

A crawling cell with DNA shown in blue and actin filaments, which are a major component of the cytoskeleton, visible in pink. Actin filaments help enable cells to crawl. This image was captured using structured illumination microscopy.

Detailed three-dimensional reconstruction of a tubular matrix in a thin section of the peripheral endoplasmic reticulum between the plasma membranes of the cell.
The endoplasmic reticulum (ER) is a continuous membrane that extends like a net from the envelope of the nucleus outward to the cell membrane. The ER plays several roles within the cell, such as in protein and lipid synthesis and transport of materials between organelles.
Shown here is a three-dimensional representation of the peripheral ER microtubules. Related to images 5855 and 5856

Yeast cells entering mitosis, also known as cell division. The green and magenta dots are two proteins that play important roles in mitosis. They show where the cells will split. This image was captured using wide-field microscopy with deconvolution.

Related to images 6792, 6793, 6794, 6797, 6798, and videos 6795 and 6796.

These developing mouse nerve cells have a nucleus (yellow) surrounded by a cell body, with long extensions called axons and thin branching structures called dendrites. Electrical signals travel from the axon of one cell to the dendrites of another.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

These cells are induced stem cells made from human adult skin cells that were genetically reprogrammed to mimic embryonic stem cells. The induced stem cells were made potentially safer by removing the introduced genes and the viral vector used to ferry genes into the cells, a loop of DNA called a plasmid. The work was accomplished by geneticist Junying Yu in the laboratory of James Thomson, a University of Wisconsin-Madison School of Medicine and Public Health professor and the director of regenerative biology for the Morgridge Institute for Research.

The green in this image highlights a protein called TonB, which is produced by many gram-negative bacteria, including those that cause typhoid fever, meningitis and dysentery. TonB lets bacteria take up iron from the host's body, which they need to survive. More information about the research behind this image can be found in a Biomedical Beat Blog posting from August 2013.

This image shows an osteosarcoma cell with DNA in blue, energy factories (mitochondria) in yellow, and actin filaments—part of the cellular skeleton—in purple. One of the few cancers that originate in the bones, osteosarcoma is rare, with about a thousand new cases diagnosed each year in the United States.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

A scanning electron microscope image of an activated mast cell. This image illustrates the interesting topography of the cell membrane, which is populated with receptors. The distribution of receptors may affect cell signaling. This image relates to a July 27, 2009 article in Computing Life.

Groups of Staphylococcus aureus bacteria (blue) attached to a microstructured titanium surface (green) that mimics an orthopedic implant used in joint replacement. The attachment of pre-formed groups of bacteria may lead to infections because the groups can tolerate antibiotics and evade the immune system. This image was captured using a scanning electron microscope.

More information on the research that produced this image can be found in the Antibiotics paper "Free-floating aggregate and single-cell-initiated biofilms of Staphylococcus aureus" by Gupta et al.

Related to image 6804 and video 6805.

Cytoplasmic linker protein (CLIP)-170 is a microtubule plus-end-tracking protein that regulates microtubule dynamics and links microtubule ends to different intracellular structures. In this movie, the gene for CLIP-170 has been fused with green fluorescent protein (GFP). When the protein is expressed in cells, the activities can be monitored in real time. Here, you can see CLIP-170 streaming towards the edges of the cell.

The worm Caenorhabditis elegans is a popular laboratory animal because its small size and fairly simple body make it easy to study. Scientists use this small worm to answer many research questions in developmental biology, neurobiology, and genetics. This image, which was taken with transmission electron microscopy (TEM), shows a cross-section through C. elegans, revealing various internal structures.

The image is from a figure in an article published in the journal eLife. There is an annotated version of this graphic at 5760.

Cells move forward with lamellipodia and filopodia supported by networks and bundles of actin filaments. Proper, controlled cell movement is a complex process. Recent research has shown that an actin-polymerizing factor called the Arp2/3 complex is the key component of the actin polymerization engine that drives amoeboid cell motility. ARPC3, a component of the Arp2/3 complex, plays a critical role in actin nucleation. In this photo, the ARPC3+/+ fibroblast cells were fixed and stained with Alexa 546 phalloidin for F-actin (red), Arp2 (green), and DAPI to visualize the nucleus (blue). Arp2, a subunit of the Arp2/3 complex, is localized at the lamellipodia leading edge of ARPC3+/+ fibroblast cells. Related to images 3329, 3330, 3331, 3332, and 3333.

In this image of a stained fruit fly ovary, the ovary is packed with immature eggs (with DNA stained blue). The cytoskeleton (in pink) is a collection of fibers that gives a cell shape and support. The signal-transmitting molecules like STAT (in yellow) are common to reproductive processes in humans. Researchers used this image to show molecular staining and high-resolution imaging techniques to students.

It has been said that gastrulation is the most important event in a person's life. This part of early embryonic development transforms a simple ball of cells and begins to define cell fate and the body axis. In a study published in Science magazine, NIGMS grantee Bob Goldstein and his research group studied how contractions of actomyosin filaments in C. elegans and Drosophila embryos lead to dramatic rearrangements of cell and embryonic structure. In these images, myosin (green) and plasma membrane (red) are highlighted at four timepoints in gastrulation in the roundworm C. elegans. The blue highlights in the top three frames show how cells are internalized, and the site of closure around the involuting cells is marked with an arrow in the last frame. See related image 3297.

Cross section of human skeletal muscle. Image taken with a confocal fluorescent light microscope.

Cells move forward with lamellipodia and filopodia supported by networks and bundles of actin filaments. Proper, controlled cell movement is a complex process. Recent research has shown that an actin-polymerizing factor called the Arp2/3 complex is the key component of the actin polymerization engine that drives amoeboid cell motility. ARPC3, a component of the Arp2/3 complex, plays a critical role in actin nucleation. In this photo, the ARPC3+/+ fibroblast cells were fixed and stained with Alexa 546 phalloidin for F-actin (red), mDia1 (green), and DAPI to visualize the nucleus (blue). mDia1 is localized at the lamellipodia of ARPC3+/+ fibroblast cells. Related to images 3328, 3329, 3331, 3332, and 3333.

Thin, hair-like biological structures called cilia are tiny but mighty. Each one, made up of more than 600 different proteins, works together with hundreds of others in a tightly-packed layer to move like a crowd at a ball game doing "the wave." Their synchronized motion helps sweep mucus from the lungs and usher eggs from the ovaries into the uterus. By controlling how fluid flows around an embryo, cilia also help ensure that organs like the heart develop on the correct side of your body.

Scanning electron micrograph of just-divided HeLa cells. Zeiss Merlin HR-SEM. See related images 3519, 3520, 3521, 3522.

These images show frog cells in interphase. The cells are Xenopus XL177 cells, which are derived from tadpole epithelial cells. The microtubules are green and the chromosomes are blue. Related to 3442.

This image shows collagen, a fibrous protein that's the main component of the extracellular matrix (ECM). Collagen is a strong, ropelike molecule that forms stretch-resistant fibers. The most abundant protein in our bodies, collagen accounts for about a quarter of our total protein mass. Among its many functions is giving strength to our tendons, ligaments and bones and providing scaffolding for skin wounds to heal. There are about 20 different types of collagen in our bodies, each adapted to the needs of specific tissues.

Cell-like compartments that spontaneously emerged from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Image created using confocal microscopy.

For more photos of cell-like compartments from frog eggs view: 6584, 6585, 6586, 6592, and 6593.

For videos of cell-like compartments from frog eggs view: 6587, 6588, 6589, and 6590.

This eerily glowing blob isn't an alien or a creature from the deep sea--it's a mouse embryo just eight and a half days old. The green shell and core show a protein called Smad4. In the center, Smad4 is telling certain cells to begin forming the mouse's liver and pancreas. Researchers identified a trio of signaling pathways that help switch on Smad4-making genes, starting immature cells on the path to becoming organs. The research could help biologists learn how to grow human liver and pancreas tissue for research, drug testing and regenerative medicine. In addition to NIGMS, NIH's National Institute of Diabetes and Digestive and Kidney Diseases also supported this work.