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Beak-nosed mice a clue to human cleft palate

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Gaborn

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MICE with a beak-like nose have been engineered to help explain how the human face might form in the womb. The hope is that this could lead to the development of therapies for babies born with facial defects, and adult facial reconstruction.

Trevor Williams at the University of Colorado Denver in Aurora and colleagues genetically modified mouse embryos to boost or inhibit the activity of a gene that produces a protein called beta-catenin in the outermost cell layer, or ectoderm, of the embryo - destined to form the skin and face.

In mice, genes activated further downstream by beta-catenin are associated with the timing and growth of the face. Mutations in the human version of some of the genes in this pathway, such as MSX1, are associated with facial disorders, such as clefting of the lip and palate.

Reducing or increasing the production of beta-catenin resulted in "drastic differences" in cranial morphology in both groups of mice. Embryos that lacked beta-catenin "lost their lower jaw and ended up with a very thin nose that looks like a chicken beak", says Williams (Developmental Biology, DOI: 10.1016/j.ydbio.2010.11.012).

Conversely, boosting beta-catenin created embryos with large facial prominences made of cartilage, along with a wider nose resembling a muzzle.

After following their development in the womb, the team sacrificed both groups of mice as they would not have been able to eat properly.

In 2002, mouse embryos were engineered to produce more beta-catenin in cells which go on to form neurons. These mice developed bigger brains, because the protein encouraged cells to divide. In the current study, no difference in cellular division was detected in either group, suggesting that in the ectoderm beta-catenin controls cell movement rather than replication.

It is likely that several key proteins, including beta-catenin, help coordinate the action of thousands of genes that ensure a face materialises from early embryonic tissue.

If researchers can "get a handle" on these proteins they could manipulate them, says Williams. In doing so, they "could rescue deformed facial development [in children]" and, in combination with stem cells, potentially rebuild a face after an accident. "We would have a shelf full of signalling molecules that we could go to, to manipulate facial development," he says.

Williams suggests that it might be possible to intervene pharmacologically where fetuses are identified as at risk of deformity, for example, by using signalling proteins to stimulate the development of a nose or chin.

For adults with facial injuries, "the idea would be to reprogram stem cells in association with signalling molecules to mould facial development", Williams says.

Peter Farlie, a developmental biologist at Murdoch Children's Research Institute in Parkville, Victoria, Australia, says the study shows the important role ectoderm cells play in instructing underlying cells to become bone and cartilage, as well as telling them what shape the structure they form should take.

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Very cool stuff, but "sacrificed," really? Did they give them to the Sun God, He-Who-Shines-Upon-All-The-Mighty-And-Beneficent Ra?
 

McNei1y

Member
Williams suggests that it might be possible to intervene pharmacologically where fetuses are identified as at risk of deformity, for example, by using signalling proteins to stimulate the development of a nose or chin.

For adults with facial injuries, "the idea would be to reprogram stem cells in association with signalling molecules to mould facial development", Williams says.

science is fucking awesome. Make this work Mr. and Mrs. Scientists!!
 
In the animal facilities I've been in, a lot of them are "sacrificed" by being put in a clear box with a CO2 line and they're suffocated.
 

Artanisix

Member
I have a cleft lip/palate, and I still haven't finished all of my surgeries yet (21 years of age). It doesn't bother me so much anymore, but if this means I could have been more confident through to the age of 17, then I am stoked for those who potentially may be born with facial deformities in the future.
 
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