̽��ֱ�� of Cambridge - Frogs

Scientists find new type of cell that helps tadpoles’ tails regenerate

ta385 — Fri, 17 May 2019 08:00:00 +0000

It has long been known that some animals can regrow their tails following amputation – Aristotle observed this in the fourth century B.C. – but the mechanisms that support such regenerative potential remain poorly understood.

Using ‘single-cell genomics’, scientists at the Wellcome Trust/ Cancer Research UK Gurdon Institute at the ̽��ֱ�� of Cambridge developed an ingenious strategy to uncover what happens in different tadpole cells when they regenerate their tails.

Recent Cambridge-led advances in next-generation sequencing mean that scientists can now track which genes are turned on (being expressed) throughout a whole organism or tissue, at the resolution of individual cells. This technique, known as ‘single-cell genomics’, makes it possible to distinguish between cell types in more detail based on their characteristic selection of active genes.

These breakthroughs are beginning to reveal a map of cellular identities and lineages, as well as the factors involved in controlling how cells choose between alternative pathways during embryo development to produce the range of cell types in adults.

Using this technology, Can Aztekin and Dr Tom Hiscock – under the direction of Dr Jerome Jullien – made a detailed analysis of cell types involved in regeneration after damage in African clawed frog tadpoles (Xenopus laevis). Details are published today in the journal Science.

Dr Tom Hiscock says: “Tadpoles can regenerate their tails throughout their life; but there is a two-day period at a precise stage in development where they lose this ability. We exploited this natural phenomenon to compare the cell types present in tadpoles capable of regeneration and those no longer capable.”

̽��ֱ��researchers found that the regenerative response of stem cells is orchestrated by a single sub-population of epidermal (skin) cells, which they termed Regeneration-Organizing Cells, or ROCs.

Can Aztekin says: “It’s an astonishing process to watch unfold. After tail amputation, ROCs migrate from the body to the wound and secrete a cocktail of growth factors that coordinate the response of tissue precursor cells. These cells then work together to regenerate a tail of the right size, pattern and cell composition.”

In mammals, many tissues such as the skin epidermis, the intestinal epithelium and the blood system, undergo constant turnover through life. Cells lost through exhaustion or damage are replenished by stem cells. However, these specialised cells are usually dedicated to tissue sub-lineages, while the ability to regenerate whole organs and tissues has been lost in all but a minority of tissues such as liver and skin.

Professor Benjamin Simons, a co-author of the study says: “Understanding the mechanisms that enable some animals to regenerate whole organs represents a first step in understanding whether a similar phenomenon could be reawakened and harnessed in mammalian tissues, with implications for clinical applications.”

Reference:

C. Aztekin et al. ‘Identification of a regeneration- organizing cell in the Xenopus tail.’ Science (17 May 2019). DOI: 10.1126/science.aav9996

Researchers at the ̽��ֱ�� of Cambridge have uncovered a specialised population of skin cells that coordinate tail regeneration in frogs. These ‘Regeneration-Organizing Cells’ help to explain one of the great mysteries of nature and may offer clues about how this ability might be achieved in mammalian tissues.

It’s an astonishing process to watch unfold

Can Aztekin

Can Aztekin, Wellcome Trust Cancer Research UK Gurdon Institute, Cambridge.

Regeneration-organizing cells outline the advancing edge of a regenerating tail of a tadpole.

Acknowledgements

This research was funded by the ̽��ֱ�� of Cambridge, the Cambridge Trust and the Wellcome Trust; and supported by the European Molecular Biology Organization, the Royal Society, the European Molecular Biology Laboratory, and Cancer Research UK.

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Why Spider-Man can’t exist: Geckos are ‘size limit’ for sticking to walls

jeh98 — Mon, 18 Jan 2016 20:05:00 +0000

A new study, published today in PNAS, shows that in climbing animals ranging in size from mites to geckos, the percentage of body surface covered by adhesive footpads increases as body size increases, setting a limit to the size of animal using this strategy because larger animals would require impossibly big feet.

Dr David Labonte and his colleagues in the ̽��ֱ�� of Cambridge’s Department of Zoology found that tiny mites use approximately 200 times less of their body surface area for adhesive pads than geckos, nature's largest adhesion-based climbers. And humans? We’d need as much as 40% of our total body surface, or roughly 80% of our front, to be covered in sticky footpads if we wanted to do a convincing Spider-Man impression.

Once an animal is so big that a substantial fraction of its body surface would need to be sticky footpads, the necessary morphological changes would make the evolution of this trait impractical, suggests Labonte.

“If a human, for example, wanted to climb up a wall the way a gecko does, we’d need impractically large sticky feet – and shoes in European size 145 or US size 114,”says Walter Federle, senior author also from Cambridge’s Department of Zoology.

“As animals increase in size, the amount of body surface area per volume decreases – an ant has a lot of surface area and very little volume, and an elephant is mostly volume with not much surface area” explains Labonte.

“This poses a problem for larger climbing animals because, when they are bigger and heavier, they need more sticking power, but they have comparatively less body surface available for sticky footpads. This implies that there is a maximum size for animals climbing with sticky footpads – and that turns out to be about the size of a gecko.”

̽��ֱ��researchers compared the weight and footpad size of 225 climbing animal species including insects, frogs, spiders, lizards and even a mammal.

“We covered a range of more than seven orders of magnitude in body weight, which is roughly the same weight difference as between a cockroach and Big Ben” says Labonte.

“Although we were looking at vastly different animals – a spider and a gecko are about as different as a human is to an ant – their sticky feet are remarkably similar,” says Labonte.

“Adhesive pads of climbing animals are a prime example of convergent evolution – where multiple species have independently, through very different evolutionary histories, arrived at the same solution to a problem. When this happens, it’s a clear sign that it must be a very good solution.”

There is one other possible solution to the problem of how to stick when you’re a large animal, and that’s to make your sticky footpads even stickier.

“We noticed that within some groups of closely related species pad size was not increasing fast enough to match body size yet these animals could still stick to walls,” says Christofer Clemente, a co-author from the ̽��ֱ�� of the Sunshine Coast.

“We found that tree frogs have switched to this second option of making pads stickier rather than bigger. It’s remarkable that we see two different evolutionary solutions to the problem of getting big and sticking to walls,” says Clemente.

“Across all species the problem is solved by evolving relatively bigger pads, but this does not seem possible within closely related species, probably since the required morphological changes would be too large. Instead within these closely related groups, the pads get stickier in larger animals, but the underlying mechanisms are still unclear. This is a great example of evolutionary constraint and innovation.”

̽��ֱ��researchers say that these insights into the size limits of sticky footpads could have profound implications for developing large-scale bio-inspired adhesives, which are currently only effective on very small areas.

“Our study emphasises the importance of scaling for animal adhesion, and scaling is also essential for improving the performance of adhesives over much larger areas. There is a lot of interesting work still to be done looking into the strategies that animals use to make their footpads stickier - these would likely have very useful applications in the development of large-scale, powerful yet controllable adhesives,” says Labonte.

This study was supported by research grants from the UK Biotechnology and Biological Sciences Research Council (BB/I008667/1), the Human Frontier Science Programme (RGP0034/2012), the Denman Baynes Senior Research Fellowship, and a Discovery Early Career Research Fellowship (DE120101503).

Reference:

Labonte, D et al "Extreme positive allometry of animal adhesive pads and the size limits of adhesion-based climbing." PNAS 18 January 2016. DOI: 10.1073/pnas.1519459113

Inset images: Vallgatan 21D, Gothenburg, Sweden (photo by Gudbjörn Valgeirsson, footprints added by Cedric Bousquet, ̽��ֱ�� of Cambridge); How sticky footpad area changes with size (David Labonte); Diversity of sticky footpads (David Labonte).

Latest research reveals why geckos are the largest animals able to scale smooth vertical walls – even larger climbers would require unmanageably large sticky footpads. Scientists estimate that a human would need adhesive pads covering 40% of their body surface in order to walk up a wall like Spider-Man, and believe their insights have implications for the feasibility of large-scale, gecko-like adhesives.

If a human wanted to climb up a wall the way a gecko does, we’d need impractically large sticky feet – and shoes in European size 145

Walter Federle

A Hackmann & D Labonte

Gecko and ant

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