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Its Midpoint

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Its Midpoint A Worm Seeks Its Midpoint Artists and architects of all eras have been inspired by symmetry in nature. This is hardly surprising, as symmetry is considered the epitome of beauty – and mirror symmetry is the absolute gold standard. Jochen Rink from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden is seeking to discover how organisms define the mirror plane and thereby fulfill the basic prerequisite for a symmetrical body structure. To do this he studies flatworms and their astonishing ability to regenerate missing body parts. Planarians are almost impossible to kill – at least by chopping them into pieces. A complete worm can form from even the smallest parts; all that is required is the formation of a new body axis. FOCUS_Symmetry TEXT CATARINA PIETSCHMANN hile most of the worms with their red wing cases with flashy try during regeneration – regardless of sit motionless at the black dots. We don’t need all that. Give whether the original animal was divid- bottom of their cul- us something else instead: eternal youth! ed into two pieces or twenty. For exam- ture dish, a few do lei- For the price of eternal youth, some ple, strips of tissue that are cut from the surely rounds through flatworm species even forego sex. The side of a flatworm initially curl up into theirW pool. With barely perceptible species that reproduce asexually are a tight corkscrew spiral and develop movements, they glide elegantly on practically immortal, because every into completely independent organ- thousands of microscopic cilia across tenth cell in the worm body is actually isms in a matter of days. This distin- the bottom of the plastic container they a stem cell that can generate all of the guishes flatworms from other regener- call home. This would be quite a majes- different cell types indefinitely. For this ation specialists, such as the axolotl: tic sight were it not for their large and reason, planarians self-renew constant- although these salamanders can regen- rather comical eyes. Planarians squint ly. For every dividing stem cell, a spe- erate missing body parts, organs and and look, not ahead, but rigidly upward. cialized cell dies, so the shape and size even parts of the brain, the cut-off piece Over 60 species of these flatworms, of the worms remains unchanged. never develops into a new animal, but which are all indeed very flat, inhabit a rather perishes. specially reserved breeding room here ONE BECOMES TWO Something the two animals do have in Dresden. They were collected from in common, though, is the symmetry all over the world and include some To reproduce, all they have to do is of their body plans. The foundations of very rare eyeless specimens from caves, hold on tight with the tip of their tail symmetry are already laid in the early and others that have a string of eyes while the head moves on. “After a few embryonic stages. Also the process of along the edge of their bodies. Flat- hours, the body tears apart and two regeneration in planarians must ensure worms are usually between 0.8 and 2.5 complete worms regenerate from the that the resulting body is symmetrical, centimeters in length, but there are also two pieces in just two weeks,” explains or that the new parts re-complete the some veritable giants that measure one Jochen Rink from the Max Planck Insti- symmetry of the existing body. “This meter in length. They usually come in tute in Dresden. This makes planarians so-called bilateral symmetry – two mir- different shades of brown or black, but one of the most sought-after test ob- ror-image body halves – is a basic struc- some also have distinctive dots or jects in stem cell research. Their ex- tural principle of higher organisms,” stripes. They are easy to care for in the traordinary regeneration capacity may says Rink. laboratory and pounce on the bits of hold the key to eternal youth and to Bilateral symmetry requires, first, an calf liver or mealworms fed to them in cures for many illnesses. axis of symmetry, known as the mid- their plastic boxes. But there is something else about line. But how does an organism actual- Given their bizarre appearance, one flatworms that fascinates Rink: not ly define a line? It is already known that might almost think they made a deal only can they build a complete organ- evolution has come up with different with nature millions of years ago: Let ism from any random tissue piece, they ways of doing this. In vertebrates, for Photo: Eduard Solà/CC-BY-SA-3.0 others be beautiful, like the ladybirds even manage to restore perfect symme- example, the dividing cells of the early 3 | 16 MaxPlanckResearch 19 xxxxxxxxxxxx 20 MaxPlanckResearch 3 | 16 FOCUS_Symmetry Left page Planarians are easy to care for: Apart from feeding and occasional water changes, Jochen Rink (top left) doesn’t have to do much for them. They live in standard plastic household containers in the laboratory of the Max Planck Institute in Dresden (top right). They can reproduce very rapidly in these containers (bottom). This page Planarians need the hedgehog signaling pathway to regenerate lost tissue. A middle piece (left) usually forms a head with a brain (blue) and the tail with two intestinal strands (green). If there is not enough hedgehog available (center), a normal head grows, but no tail. If there is too much hedgehog (right), a complete tail is formed instead of the head. embryo migrate and gradually envelop and “bottom” signals suppress each of symmetry in an organism malfunc- the yolk mass like a tight-fitting hat. A other, but because the belly signals are tions. Deformed lambs with only one subset of these cells reverses direction stronger, all that remains of the top eye were born on a few meadows in Cal- at a defined point, the so-called orga- signals in the end is a clearly defined ifornia. Like the Cyclops in Greek my- nizer, and marches back up against the line along the back, which again be- thology, their eye sat in the middle of flow on the inside of the hat. This pro- comes part of the midline of the their head. It emerged that the ewes had duces a hemisphere composed of two emerging fly body. eaten corn lilies. These plants contain a cell layers. And what about planarians? Rink toxin that inhibits recognition of the and his colleagues started by looking hedgehog signaling protein in embryon- STARTING POINT FOR THE for genes that are active only at the ic cells. Surprisingly, the defect was lim- MIDLINE midline. The genes they encountered ited to the lambs’ heads. The animals, here included the BAMBI and Slit genes, which died soon after birth, had four “The reversal point later turns into the both of which are active only in cells normally formed legs. midline of the body, and the head and located exactly along the midline: “If we disrupt the hedgehog signal- tail form at its opposite ends.” Signaling BAMBI is active only in a narrow strip ing pathway in planarians, something networks in the cells control this process along the back, and Slit marks a broad- similar happens,” reports Rink. He and by switching certain genes on and off at er V-shaped strip extending all the way his colleagues varied the strength of the the right time. In short, nature proceeds from the head to the tip along the ani- hedgehog signal in the worm body, cut thus: a point is defined from which the mals’ belly side. Thus, the midline is de- off the head and tail, and observed the cells migrate in opposite directions, and fined, not by a single cell type, but by regenerating pieces. If the piece had far voilà – the line is created. multiple types. Here, too, nature prob- too little of the hedgehog signal, a per- The fruit fly Drosophila takes a dif- ably uses the same molecular mecha- fect new head developed, but the tail ferent approach to midline formation. nisms throughout the animal kingdom, was severely truncated; if too much of Its embryos aren’t spherical, but rath- as Slit is also active along the midline the hedgehog signal was present, the er cigar-shaped. Signaling substances in flies and humans. regeneration of the tail was perfectly in the cells define “top” and “bottom,” In the early 1960s, biologists acci- fine, but the pieces regenerated a tail in which correspond to the back and bel- dentally discovered the dramatic conse- place of the head. And if the hedgehog xxxxxxxxxxxx Photos: Max Planck Institute of Molecular Cell Biology and Genetics (4) ly halves of the future embryo. “Top” quences that arise when the formation signal was only slightly raised, worms 3 | 16 MaxPlanckResearch 21 FOCUS_Symmetry Day 0 Day 2 Day 6 Day 10 1 mm Day 15 1 mm with stunted and eyeless heads or, line. If the head isn’t fully formed, imal and serves as both the mouth and again, one-eyed Cyclops worms, regen- problems with the midline arise, and the anus. The midline doesn’t extend erated. Except that in the case of the result in one-eyed animals.” Clearly, to the tip of the tail until the digestive lambs, the one-eyed lambs had too lit- the signaling systems that designate the tract is fully formed. The cells seem to tle of the hedgehog signal. midline are so finely tuned that they operate like a construction team that don’t tolerate any kind of disturbance. completes the work at one location be- NEURAL PATHWAYS FORM A LOOP In order to track how a new midline fore moving on to the next.
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