Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cleft palate in fetal mice prevented by treating

13.02.2007
Mice engineered to have cleft palates can be rescued in utero by injecting the mothers with a small molecule to correct the defect, say scientists at the Stanford University School of Medicine and Lucile Packard Children's Hospital.

In addition to shedding light on the biology of cleft palate, the research raises hopes that it may one day be possible to prevent many types of human birth defects by using a similar vaccination-type technique in pregnant women likely to have affected fetuses.

"This is a really important baby step that opens the door to the development of fetal therapies," said pediatric craniofacial surgeon Michael Longaker, MD. "Our hope and expectation is that patients at Packard Children's and other institutions will benefit as this basic advance is translated into something that will eventually make a significant difference for this and other birth defects."

Longaker is the senior author of the study, which will be published in the Feb. 11 advance online edition of Nature. The research is the first demonstration that a technique known as chemical genetics ­ in which small molecules are used to modify gene expression or protein activity ­ can reach a fetus when administered to a pregnant animal.

... more about:
»Fetus »Liu »Longaker »fetal »palate

"It's such a cool concept," said Longaker, professor of medicine and a leader in Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "We injected a small molecule into mom, and it goes into the embryo and works. There are tremendous implications to the idea of preventing conditions in unborn patients rather than trying to treat them after birth." Cleft defects are the second-most common birth defect worldwide and affect about one in 2,000 births.

Longaker, who spent several years in fetal surgery working to design surgical approaches for life-threatening defects prior to coming to Stanford, said the concept of noninvasively preventing these defects by treating the mother is something that was unthinkable when he first began his work. "This is a great example of expectations changing as technology evolves," he said.

For this study, co-author and postdoctoral scholar Karen Liu, PhD, used a short amino-acid tag to disrupt the function of a protein called GSK-3 beta. GSK-3 beta function is important in a variety of biological processes, and mice with the tagged protein exhibited many problems in utero, including cleft palates and sternum defects. However, Liu was able to reverse the defects by injecting the pregnant mice with rapamycin­a small molecule that stabilized the tag and restored the protein's function.

In addition to revealing for the first time that GSK-3 beta is important in palate formation, Liu discovered that the technique could be used to identify the specific times during development that the protein's function is required. For example, maternal rapamycin treatment between embryonic days 13.5 and 15 corrected the palate defect, but normal sternal development required functional protein between days 15.5 and 17. It's likely that the same chemical genetic approach could be applied to a variety of proteins and developmental processes to create a series of molecular snapshots of embryogenesis.

"The beauty of the technique is that it nails down the developmental window for various embryonic events," said Longaker. "We don't need to treat the mother long term, but just during the time that the organ or structure is forming."

Although promising, direct human applications of the research will require several key advances: an ability to predict which women are likely to have fetuses with birth defects before the defects occur; knowledge of an effective, small-molecule based therapy that can prevent the defect; and an accurate method of tracking fetal development to allow time-appropriate administration of the therapy.

"Over time, I expect we will have the ability to overcome these obstacles," said Longaker. "This is the true value of having one of the best children's hospitals in the country integrated within a school of medicine renowned for its research capabilities. With interdisciplinary teamwork, we may be able to develop a whole new way to prevent birth defects."

Gerald Crabtree, MD, PhD, professor of pathology and developmental biology, collaborated with Longaker and Liu on the study. Liu is supported by an NIH training program in regenerative medicine that fosters the interdisciplinary collaboration that led to the breakthrough research. "We're putting people together in the sandbox who wouldn't normally be playing together," quipped Longaker about the collaboration.

Krista Conger | EurekAlert!
Further information:
http://www.stanford.edu

Further reports about: Fetus Liu Longaker fetal palate

More articles from Life Sciences:

nachricht Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>