Their study, published in the advance online edition of Genes and Development on Nov. 17, demonstrates that vertebrate regeneration is under the control of the powerful Wnt signaling system: Activating it overcomes the mysterious barrier to regeneration in animals like chicks that can't normally replace missing limbs while inactivating it in animals known to be able to regenerate their limbs (frogs, zebrafish, and salamanders) shuts down their ability to replace missing legs and tails.
"In this simple experiment, we removed part of the chick embryo's wing, activated Wnt signaling, and got the whole limb back - a beautiful and perfect wing," said the lead author, Juan Carlos Izpisúa Belmonte, Ph.D., a professor in the Gene Expression Laboratory. "By changing the expression of a few genes, you can change the ability of a vertebrate to regenerate their limbs, rebuilding blood vessels, bone, muscles, and skin - everything that is needed."
This new discovery "opens up an entirely new area of research," Belmonte says. "Even though certain animals have lost their ability to regenerate limbs during evolution, conserved genetic machinery may still be present, and can be put to work again," he said. Previously, scientists believed that once stem cells turned into muscles, bone or any other type of cells, that was their fate for life – and if those cells were injured, they didn't regenerate, but grew scar tissue.
Manipulating Wnt signaling in humans is, of course, not possible at this point, Belmonte says, but hopes that these findings may eventually offer insights into current research examining the ability of stem cells to build new human body tissues and parts. For example, he said Wnt signaling may push mature cells go back in time and "dedifferentiate" into stem-like cells, in order to be able to then differentiate once more, producing all of the different tissues needed to build a limb.
"This is the reverse of how we currently are thinking of using stem cells therapeutically, so understanding this process could be very illuminating," he says. "It could be that we could use the Wnt signaling pathway to dedifferentiate cells inside a body at the site of a limb injury, and have them carry out the job of building a new structure."
Members of the Wnt gene family (for "wingless," originally discovered in fruit flies) are known to play a role in cell proliferative processes, like fetal growth and cancer development, and Belmonte's lab has characterized the crucial role of Wnt signaling in limb growth. In 1995, the Salk researchers were first to demonstrate that they could induce the growth of extra limbs in embryonic chicks, and in 2001, they found that the Wnt signaling system played a critical role in triggering both normal and abnormal limb growth.
The current study was designed to see if Wnt signaling also was involved in the regeneration of limbs and included three groups of vertebrates: zebrafish and salamanders, which can regenerate limbs throughout their lives; frogs, which can only regenerate new limbs during a limited period during their fetal development; and chicks, which cannot regenerate limbs.
To manipulate animals' regeneration ability, the Salk researchers used inhibitory and excitatory factors for Wnt signaling, which they delivered directly to the remaining bulge after they cut a limb from the experimental embryos.
In adult zebrafish and salamanders, they found that blocking Wnt signaling with the inhibitory factors, prevented normal regeneration. And, conversely, when they treated mutant adult zebrafish that cannot regenerate with the excitatory agent, the ability to regenerate their fins was rescued, Belmonte says.
Using an inhibitory agent on frogs before the regeneration-enabled developmental window closed resulted in loss of that ability, but treating them with the excitatory agent after they had lost their regenerative capacity induced new limb growth.
They then performed the key experiment, successfully testing the ability of an excitatory factor to produce limb regeneration in chick embryos. "The signal restarted the process, and genes that were involved in the initial development of the limb were turned back on," Belmonte says. "It is simply amazing."
The procedure was tricky, however. Belmonte noted that if Wnt signaling is activated for too long of a period in these animals, cancer results. "This has to be done in a controlled way, with just a few cells for a specific amount of time," he says. "The fact is that this pathway is involved in cell proliferation, whether it is to generate or regenerate limbs, control stem cells, or produce cancer."
Gina Kirchweger | EurekAlert!
International team discovers novel Alzheimer's disease risk gene among Icelanders
24.10.2016 | Baylor College of Medicine
New bacteria groups, and stunning diversity, discovered underground
24.10.2016 | DOE/Lawrence Berkeley National Laboratory
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Power and Electrical Engineering
24.10.2016 | Life Sciences
24.10.2016 | Life Sciences