Navigation Links
Cleft lip corrected genetically in mouse model
Date:11/28/2011

NEW YORK (Nov. 28, 2011) -- 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.


'/>"/>

Contact: Takla Boujaoude
tab2016@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

Related biology news :

1. Cleft lip and palate: Genes more important than thought?
2. First trimester smoking linked to oral clefts
3. Study finds genetic variant plays role in cleft lip
4. Metabolic defects in mice corrected with transplanted embryonic neurons
5. Genetically corrected blood cells obtained from skin cells from Fanconi anemia patients
6. Iowa State University scientists genetically increase algae biomass by more than 50 percent
7. New American Chemical Society podcast: Genetically-engineered spider silk for gene therapy
8. The establishment of genetically engineered canola populations in the US
9. University of Colorado Cancer Center genetically sequences most common bladder cancer
10. Genetically engineered spider silk for gene therapy
11. Scientist urges government ruling on genetically engineered salmon
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/3/2016)... 2016 --> ... "Automated Fingerprint Identification System Market by Component (Hardware and ... & Finance, Government, Healthcare, and Transportation) and Geography - ... is expected to be worth USD 8.49 Billion by ... and 2020. The transformation and technology evolution from the ...
(Date:2/2/2016)... 2, 2016  BioMEMS devices deployed in ... on medical screening and diagnostic applications, such ... devices that facilitate and assure continuous monitoring ... are being bolstered through new opportunities offered ... acquisition coupled with wireless connectivity and low ...
(Date:2/2/2016)... Technology Enhancements Accelerate Growth of X-ray Imaging ... and computed radiography markets in Thailand ... Indonesia (TIM). It provides an in-depth analysis ... as regional market drivers and restraints. The study offers ... market attractiveness, both for digital and computed radiography. Market ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... NJ (PRWEB) , ... February 09, 2016 , ... ... Dorman, former Vice President for Public Policy for the National Organization for Rare ... patient advocacy groups to ensure their voices are heard throughout the drug regulatory ...
(Date:2/9/2016)... Feb. 9, 2016 This market research report ... and future prospects of the market in terms of ... companies engaged in the manufacture of microbiology culture media ... with a market snapshot providing the overall information of ... report. This section also provides the overall information and ...
(Date:2/9/2016)... -- Three-Year Initiative Supports Next Generation of Medical ... Life-Changing Camp Experiences ... the lives of children born with rare diseases, as well as ... is announcing a new initiative designed to positively affect the lives ... of rare disease care. --> To mark the company,s ...
(Date:2/9/2016)... Feb. 9, 2016 ... 2016", report provides in depth insights on ... around the Protein-Tyrosine Phosphatase 1B (PTP1B) Inhibitors. ... in various stages of development including Discovery, ... III and Preregistration. Report covers the product ...
Breaking Biology Technology: