Featured Research

from universities, journals, and other organizations

Cleft lip corrected genetically in mouse model

Date:
November 28, 2011
Source:
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Summary:
Scientists have used genetic methods to successfully repair cleft lips in mice embryos specially engineered for the study of cleft lip and cleft palate. The research breakthrough may show the way to prevent or treat the conditions in humans.

Scientists at Weill Cornell Medical College used genetic methods to successfully repair cleft lips in mice embryos specially engineered for the study of cleft lip and cleft palate. The research breakthrough may show the way to prevent or treat the conditions in humans.

Cleft lip and cleft palate are among the most common birth defects, with treatment requiring multiple cycles of surgery, speech therapy and orthodontics. To date, there have been very few pre-clinical methods that allow researchers to study the molecular causes of these malformations. In particular, there has been a lack of animal models that accurately reflect the contribution of multiple genes to these congenital deformities in humans.

In a report in a recent issue of the journal Developmental Cell, Dr. Licia Selleri, associate professor of cell and developmental biology at Weill Cornell Medical College, and her co-authors report the first multigenic mouse model of cleft lip with or without cleft palate. The researchers uncovered the role of genes for Pbx (Pre-B Cell Leukemia Transcription Factor) proteins in coordinating cellular signaling behaviors crucial for the development of these abnormalities. They also discovered that altering one type of molecule within the Wnt signaling pathway (that comprises a network of proteins best known for their roles in embryogenesis) is sufficient to correct the defects.

Dr. Selleri has studied Pbx proteins for many years and has previously demonstrated their involvement in organ and skeletal development. In her latest study, she and her collaborators, including postdoctoral fellows Drs. Elisabetta Ferretti and Bingsi Li, tested whether these proteins also play a role in facial development by using mutant mice that lacked various combinations of three Pbx genes in the ectoderm, the embryonic cell layer that gives rise to the lip and nose.

The researchers found that only mutations affecting multiple Pbx genes resulted in complete cleft lip, with or without cleft palate, in all of the mouse embryos with these compound mutations. This finding differs from those of previous studies using other mammal models of these conditions, in which a mutation in a single gene produced defects in only some of the animals, Dr. Selleri says. The role of Pbx genes in the development of the shape of the face is a new and surprising finding, she adds.

Moreover, the mouse embryos with multiple Pbx mutations also had reduced or absent Wnt activity, which plays a prominent role in embryo development, within the ectoderm. Dr. Ferretti, the first author of this study, found that Pbx genes regulate a chain of signaling molecules implicated in cleft lip with or without cleft palate, including Wnt, fibroblast growth factors (FGFs), p63, and interferon regulatory factor 6 (Irf6) -- signaling pathways that exist across mammal species. Disturbances in this network lead to a decrease in programmed cell death, thereby interfering with the proper fusion of facial tissues and resulting in cleft lip.

When Dr. Li, the second author of this study, used genetic methods to restore Wnt activity in the ectoderm of mouse embryos with compound Pbx mutations, the cleft lips in all of these animals completely disappeared. "To my knowledge, this is the first time that anyone has corrected this defect in embryos, and we really show here that Wnt is a critical factor," Dr. Selleri says. "This is a very provocative result because it opens a completely new avenue of strategies for tissue repair."

To follow up on this work, Dr. Selleri plans to test whether supplying Wnt molecules to Pbx-mutated mouse embryos placed within an environment that mimics the uterus is sufficient to correct or even prevent the abnormalities. Compared with genetic manipulations, this approach of delivering Wnt signals directly to the uterus would be more realistic for implementation in humans, Dr. Selleri says. She has just initiated a collaboration with Jason Spector, assistant professor of plastic surgery at Weill Cornell Medical College and with Larry Bonassar, associate professor of biomedical engineering at Cornell University, to envision Wnt-related strategies for tissue repair, such as tissue implants that would deliver Wnt molecules to correct these defects either in utero before the birth of the fetus, or after birth without the need of many surgeries.

Additional study collaborators include Rediet Zewdu and Victoria Wells of Weill Cornell Medical College; Jean M. Hebert of Albert Einstein College of Medicine in the Bronx, N.Y.; Courtney Karner of the University of Texas, Southwestern Medical Center, in Dallas, Texas; Matthew J. Anderson of the National Cancer Institute in Frederick, Md.; Trevor Williams of the University of Colorado, Denver; Jill Dixon and Michael J. Dixon of the University of Manchester in the U.K.; and Michael J. Depew of King's College London in the U.K.

The research was supported by a Marie Curie Fellowship, the Medical Research Council in the U.K., the Royal Society, King's College London, March of Dimes and Birth Defects Foundation, the National Institutes of Health, the Cleft Palate Foundation, and the Alice Bohmfalk Trust.


Story Source:

The above story is based on materials provided by New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. Note: Materials may be edited for content and length.


Journal Reference:

  1. Elisabetta Ferretti, Bingsi Li, Rediet Zewdu, Victoria Wells, JeanM. Hebert, Courtney Karner, MatthewJ. Anderson, Trevor Williams, Jill Dixon, MichaelJ. Dixon, MichaelJ. Depew, Licia Selleri. A Conserved Pbx-Wnt-p63-Irf6 Regulatory Module Controls Face Morphogenesis by Promoting Epithelial Apoptosis. Developmental Cell, 2011; 21 (4): 627 DOI: 10.1016/j.devcel.2011.08.005

Cite This Page:

New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. "Cleft lip corrected genetically in mouse model." ScienceDaily. ScienceDaily, 28 November 2011. <www.sciencedaily.com/releases/2011/11/111128132710.htm>.
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. (2011, November 28). Cleft lip corrected genetically in mouse model. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2011/11/111128132710.htm
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. "Cleft lip corrected genetically in mouse model." ScienceDaily. www.sciencedaily.com/releases/2011/11/111128132710.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins