Navigation Links
Cleft lip corrected genetically in mouse model

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
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

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:
(Date:11/12/2015)... Nov. 11, 2015   Growing need for ... tools has been paving the way for use ... of discrete analytes in clinical, agricultural, environmental, food ... predominantly used in medical applications, however, their adoption ... due to continuous emphasis on improving product quality ...
(Date:11/9/2015)... Nov. 9, 2015  Synaptics Inc. (NASDAQ: SYNA ... announced broader entry into the automotive market with a ... the pace of consumer electronics human interface innovation. Synaptics, ... ideal for the automotive industry and will be implemented ... Europe , Japan , ...
(Date:10/29/2015)... -- Daon, a global leader in mobile biometric authentication ... version of its IdentityX Platform , IdentityX v4.0. ... have already installed IdentityX v4.0 and are seeing ... UAF certified server component as an option and ... These customers include some of the largest and most ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... -- 2 nouvelles études permettent d , ... entre les souches bactériennes retrouvées dans la plaque ... . Ces recherches  ouvrent une nouvelle voie ... efficace de l,un des problèmes de santé les ...    --> 2 nouvelles études permettent d ...
(Date:11/25/2015)... HOLLISTON, Mass. , Nov. 25, 2015 ... HART ), a biotechnology company developing bioengineered organ implants ... McGorry will present at the LD Micro "Main ... 2:30 p.m. PT. The presentation will be webcast live ... Management will also be available at the conference for ...
(Date:11/25/2015)... 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS; TSX: ... prospects remain fundamentally strong and highlights the following ... received DSMB recommendation to continue the ZoptEC Phase ... the final interim efficacy and safety data ... men with heavily pretreated castration- and Taxane-resistant prostate ...
(Date:11/25/2015)... 25, 2015 Orexigen® Therapeutics, Inc. (Nasdaq: ... a fireside chat discussion at the Piper Jaffray 27th ... . The discussion is scheduled for Wednesday, December 2, ... .  A replay will be available for 14 days ... , Julie NormartVP, Corporate Communications and Business Development , ...
Breaking Biology Technology: