The work, which was posted to the Web site of the journal Nature Medicine yesterday, is a follow-up to the team’s 2006 discovery of the cellular cause of TCS.
The team evaluated how a mutated TCOF1 gene causes the death of neural crest cells that should otherwise form most of the bone, cartilage, and connective tissue that make up the head and face during embryonic development. The loss of these cells results in abnormal development of the ear, nose, and upper and lower jaw, including cleft palate.
The team discovered that chemical inhibition of a single protein, the product of the p53 gene, could prevent the craniofacial abnormalities caused by the TCOF1 mutation. They also showed that inactivation of the p53 gene itself enabled neural crest cells to survive and form normal craniofacial structures in embryos carrying the TCOF1 mutation.
“Inhibition of the p53 protein was enough to prevent neural crest cells from dying during early embryogenesis and essentially rescue the mouse embryo from the devastating craniofacial features associated with TCS,” said Natalie Jones, Ph.D., formerly a Postdoctoral Research Associate in the Trainor Lab and first author on the paper. “The successful rescue of neural crest cell development in a congenital craniofacial anomaly such as TCS is exciting because it provides an attractive model for the prevention of other craniofacial birth defects of similar origins.”
“These findings are the culmination of years of efforts to better understand TCS,” said Paul Trainor, Ph.D., Associate Investigator and senior author on the paper. “People diagnosed with severe TCS typically undergo multiple, major reconstructive surgeries that are rarely fully corrective. The inhibition of p53 brings us much closer to our ultimate goal — preventing TCS and the suffering it causes altogether.”
“By its very nature, the progress of basic biomedical research is incremental,” said Robb Krumlauf, Ph.D., Scientific Director. “We learn a little bit at a time over many years, and each new discovery contributes to a more comprehensive understanding of a disease. This discovery by the Trainor Lab is what all of those years of hard work are about — ultimately learning enough to treat, cure, or prevent a devastating disease.”
“These meticulously performed experiments by members of the Trainor Lab and their colleagues elegantly demonstrate the power of science to address the cause and prevention of birth defects,” said William Neaves, Ph.D., President and CEO. “All of us at the Stowers Institute celebrate their landmark accomplishment.”
Marie Jennings | EurekAlert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy