To See or Not to See; The Pink Gene; Weizmann Institute Scientists Reveal How Tendons Shape Developing Bones

To See or Not to See

How do the visual images we experience, which have no tangible existence, arise out of physical processes in the brain? New research at the Weizmann Institute of Science provides evidence, for the first time, that an “ignition” of intense neural activity underlies the experience of seeing.

In research recently published in the journal Neuron, Prof. Rafael Malach and research student Lior Fisch of the Weizmann Institute’s Department of Neurobiology worked with a neurosurgeon, Dr. Itzhak Fried of Tel Aviv Sourasky Medical Center, a distinguished team of medical doctors from the Center, and Weizmann Institute students. They asked a group of epileptic patients who had had electrodes clinically implanted into their brains in preparation for surgery to volunteer for some perceptual awareness tasks. The subjects looked at a computer screen, which briefly presented a “target” image—a face, house, or man-made object. This image was followed by a “mask”—a meaningless picture for distraction—at different time intervals after the target image had been presented. This allowed the experimenter to control the visibility of the images—the patients sometimes recognized the targets and sometimes failed to do so. By comparing the electrode recordings to the patients’ reports of whether they had correctly recognized the image or not, the scientists were able to pinpoint what was happening—and when and where—in the brain as transitions in perceptual awareness took place.

Says Prof. Malach, “We found that there was a rapid burst of neural activity occurring in the high-order visual centers of the brain—centers that are sensitive to entire images of objects, such as faces—whenever patients had correctly recognized the target image.” The scientists also found that the transition from not seeing to seeing happens abruptly. According to Mr. Fisch, “When the mask was presented too soon after the target image, it ‘killed’ the visual input signals, resulting in the patients being unable to recognize the object. The patients suddenly became consciously aware of the target image at a clear threshold, suggesting that the brain needs a specific amount of time to process the input signals in order for conscious perceptual awareness to be ignited.”

This study is the first of its kind to uncover strong evidence linking ignition of bursts of neural activity to perceptual awareness in humans. More questions remain: Is this the sole mechanism involved in the transition to perceptual awareness? To what extent is it a local phenomenon? By answering such questions, scientists might begin bridging the mysterious gap between the mind and the brain.

Prof. Rafael Malach’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the S. and J. Lurje Memorial Foundation; the Benjamin and Seema Pulier Charitable Foundation, Inc; Vera Benedek, Israel; and Mary Helen Rowen, New York, NY. Prof. Malach is the incumbent of the Barbara and Morris Levinson Professorial Chair in Brain Research.

The Pink Gene

Weizmann Institute Scientists Unravel the Genetic Secrets of a Pink Tomato

Many Far Eastern diners are partial to a variety of sweet, pink-skinned tomato. Dr. Asaph Aharoni of the Weizmann Institute’s Department of Plant Sciences has now revealed the gene that is responsible for producing these pink tomatoes. Dr. Aharoni’s research focuses on plants’ thin, protective outer layers, called cuticles, which are mainly composed of fatty, wax-like substances. In the familiar red tomato, this layer also contains large amounts of antioxidants called flavonoids that are the tomatoes’ first line of defense. Some of these flavonoids also give the tomato cuticles a bright yellow cast—the color component that is missing in the translucent pink skins of the mutants.

Using a lab system that is unique in Israel, and one of only a few in the world, Dr. Aharoni and his team are able to rapidly and efficiently identify hundreds of active plant substances called metabolites. A multidisciplinary approach developed over the past decade, known as metabolomics, enables them to create a comprehensive profile of all these substances in mutant plants and compare it with that of normal ones.

The research, carried out in Dr. Aharoni’s lab by Dr. Avital Adato, Dr. Ilana Rogachev, and research student Tali Mendel, showed that the differences between pink and red tomatoes go much deeper than skin color: the scientists identified about 400 genes whose activity levels are quite a bit higher or lower in the mutant tomatoes. The largest changes, appearing in both the plant cuticle and the fruit covering, were in the production of substances in the flavonoid family. The pink tomato also has less lycopene, a red pigment known to be a strong antioxidant that has been associated with reduced risk of cancer, heart disease, and diabetes. In addition, alterations in the fatty composition of the pink tomato’s outer layer caused its cuticle to be both thinner and less flexible that a regular tomato skin.

The researchers found that all of these changes can be traced to a mutation on a single gene known as SIMYB12. This gene acts as a “master switch” that regulates the activities of a whole network of other genes, controlling the amounts of yellow pigments as well as a host of other substances in the tomato. Says Dr. Aharoni, “Since identifying the gene, we found we could use it as a marker to predict the future color of the fruit in the very early stages of development, even before the plant has flowered. This ability could accelerate efforts to develop new, exotic tomato varieties, a process that can generally take over 10 years.”

Dr. Asaph Aharoni’s research is supported by the De Benedetti Foundation-Cherasco 1547 and the Willner Family Foundation. Dr. Aharoni is the incumbent of the Adolpho and Evelyn Blum Career Development Chair of Cancer Research.

Weizmann Institute Scientists Reveal How Tendons Shape Developing Bones

Bones, muscles, and tendons work together to provide the perfect balance between stability and movement in the skeleton. Now, Weizmann Institute scientists have shown that this partnership begins in the embryo, when the bones are still taking shape. Their study, published in a recent issue of Developmental Cell, describes a previously unrecognized interaction between tendons and bones that drives the development of a strong skeletal system.

“Our skeleton, with its bones, joints, and muscle connections, serves us so well in our daily lives that we hardly pay attention to this extraordinary system,” says Dr. Elazar Zelzer of the Weizmann Institute’s Department of Molecular Genetics. “Although previous research has uncovered mechanisms that contribute to the development and growth of each component of this complex and wonderfully adaptable organ system, specific interactions between bones, muscles, and tendons that drive the assembly of the musculoskeletal system are not fully understood.”

Dr. Zelzer, research student Einat Blitz, Sergey Viukov, and colleagues, were interested in uncovering the molecular mechanisms that regulate the formation of bone ridges—bony protuberances that provide a stable anchoring point for the tendons that connect muscles with bones. Bone ridges are critical for the skeleton’s ability to cope with the considerable mechanical stresses exerted by the muscles. The researchers used embryonic mouse skeletons to study a bone ridge called the deltoid tuberosity, located on the humerus bone in the arm.

They discovered, to their surprise, that rather than being shaped by processes within the skeleton, bone-ridge formation was directly regulated by tendons and muscles in a two-phase procedure. First, the embryonic tendons initiated bone-ridge formation by attaching to the skeleton. This interaction induced the tendon cells to express a specific protein called scleraxis, which, in turn, led to the production of another protein, BMP4—a molecule involved in the onset of bone formation. Blocking BMP4 production in tendon cells prevented deltoid tuberosity bone-ridge formation. In the second phase, the subsequent growth and ultimate size of the deltoid tuberosity was directly regulated by muscle activity.

The results demonstrate that tendons play an active role in initiating bone-ridge patterning. According to Dr. Zelzer, “These findings provide a new perspective on the regulation of skeletogenesis in the context of the musculoskeletal system, and they shed light on an important mechanism that underlies the assembly of this system.”

Dr. Elazar Zelzer’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the Helen and Martin Kimmel Institute for Stem Cell Research; the Kirk Center for Childhood Cancer and Immunological Disorders; the David and Fela Shapell Family Center for Genetic Disorders Research; the estate of Rubin Feryszka; the estate of George Liebert; and the estate of Lela London. Dr. Zelzer is the incumbent of the Martha S. Sagon Career Development Chair.