About one in ten thousand babies is born with an abnormally small head. The cause for this disorder – which is known as microcephaly – is a defect in the develoment of the embryonic brain. Children with microcephaly are severely retarded and their life expectancy is low. Certain cases of autism and schizophrenia are also associated with the dysregulation of brain size.
Comparison of the size of a normal brain (left) and a microcephalic brain (right). Drawing based on coronal sections of human brains.
Genetically altered mouse embryo at the age of 12 days. Cells that produce the protein TUBB5 light up in green (most obviously in the developing brain).
The causes underlying impaired brain development can be environmental stress (such as alcohol abuse or radiation) or viral infections (such as rubella) during pregnancy. In many cases, however, a mutant gene causes the problem.
David Keays, a group leader at the IMP, has now found a new gene which is responsible for Microcephaly. Together with his PhD-student Martin Breuss, he was able to identify TUBB5 as the culprit. The gene is responsible for making tubulins, the building blocks of the cell’s internal skeleton. Whenever a cell moves or divides, it relies on guidance from this internal structure, acting like a scaffold.
The IMP-researchers, together with collaborators at Monash University (Victoria, Australia), were able to interfere with the function of the TUBB5 in the brains of unborn mice. This led to massive disturbances in the stem cell population and impaired the migration of nerve cells. Both, the generation of large numbers of neurons from the stem cell reservoir and their correct positioning in the cortex, are essential for the development of the mammalian brain.
To determine whether the findings are also relevant in humans, David Keays collaborates with clinicians from the Paris-Sorbonne University. The French team led by Jamel Chelly, examined 120 patients with pathological brain structures and severe disabilities. Three of the children were found to have a mutated TUBB5-gene.
This information will prove vital to doctors treating children with brain disease. It will allow the development of new genetic tests which will form the basis of genetic counseling, helping parents plan for the future. By understanding how different genes cause brain disorders, it is hoped that one day scientists will be able to create new drugs and therapies to treat them.
The new findings by the IMP-researchers are published in the current issue of the journal “Cell Reports”. For David Keays, understanding the function of TUBB5 is the key to understanding brain development. “Our project shows how research in the lab can help improve lives in the clinic”, he adds.
The paper "Mutations in the â-tubulin Gene TUBB5 Cause Microcephaly with Structural Brain Abnormalities" is published on December 13, 2012, in the online-Journal Cell Reports.About the IMP
Dr. Heidemarie Hurtl | idw
Molecular Spies Sabotage a Protein's Activities in Specific Cellular Compartments
20.04.2015 | Johns Hopkins Medicine
Evolution puts checks on virgin births
20.04.2015 | Okinawa Institute of Science and Technology (OIST) Graduate University
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and the University of Konstanz are working on storing and processing information on the level of single molecules to create the smallest possible components that will combine autonomously to form a circuit. As recently reported in the academic journal Advanced Science, the researchers can switch on the current flow through a single molecule for the first time with the help of light.
Dr. Artur Erbe, physicist at the HZDR, is convinced that in the future molecular electronics will open the door for novel and increasingly smaller – while also...
Cells of the vascular system of vertebrates can fuse with themselves. This process, which occurs when a blood vessel is no longer necessary and pruned, has now been described on the cellular level by Prof. Markus Affolter from the Biozentrum of the University of Basel. The findings of this study have been published in the journal “PLoS Biology”.
The vascular system is the supply network of the human organism and delivers oxygen and nutrients to the last corners of the body. So far, research on the...
Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a supermassive black hole in a distant galaxy
Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a...
A team of physicists from MPQ, Caltech, and ICFO proposes the combination of nano-photonics with ultracold atoms for simulating quantum many-body systems and creating new states of matter.
Ultracold atoms in the so-called optical lattices, that are generated by crosswise superposition of laser beams, have been proven to be one of the most...
According to new research out of the Texas A&M Health Science Center College of Medicine, that is indeed the case. Chetan Jinadatha, M.D., M.P.H., assistant...
13.04.2015 | Event News
25.03.2015 | Event News
19.03.2015 | Event News
20.04.2015 | Physics and Astronomy
20.04.2015 | Architecture and Construction
20.04.2015 | Physics and Astronomy