Is more of a good thing better? A gene known as LIS1 is crucial for ensuring the proper placement of neurons in the developing brain.
When an LIS1 gene is missing, brains fail to develop their characteristic folds; babies with lissencephaly, or “smooth brain,” are born severely mentally retarded. But new research by Prof. Orly Reiner of the Institute’s Molecular Genetics Department, which recently appeared in Nature Genetics, shows that having extra LIS1 genes can cause problems as well.
Reiner was the first to discover LIS1’s tie to lissencephaly, in 1993. Her latest study shows that LIS1 works by helping to determine polarity in the cell – how the various organelles are arranged inside the cell, as well as where it connects to neighboring cells. Neurons alter their polarity several times during development, especially when they take on an elongated shape and migrate to new locations in the brain.
But what if, rather than too little, the body has too much LIS1? One of the surprises to come out of the recent spate of post-human-genome research is the number of genes that can be repeated or deleted in an individual’s genome. Most extra copies of genes may be no more harmful than a computer backup disk, but scientists have been finding that some repeats can cause disease.
Research associate Dr. Tamar Sapir and lab technician Talia Levy, working in Reiner’s lab, developed a mouse model in which additional LIS1 protein was produced in the brain. The scientists found that the brains of these mice were a bit smaller than average. On closer inspection, they discovered a range of subtle changes in cell polarity and movement: nuclei within the proliferating zone tended to move faster, but with less control; rates of cell death were higher; and various factors in the cell became more disordered.
Reiner then asked whether their findings might apply to humans. Together with Jim Lupski and Drs. Weimin Bi and Oleg A. Shchelochkov of the Baylor College of Medicine in Houston, Texas, they searched through blood samples using a technique that matches a patient’s DNA with control DNA to identify additions or deletions in its sequence. They identified seven individuals with extra copies of either LIS1 or adjacent genes that are also involved in brain development. All suffered developmental abnormalities. Two of the patients – children with a second LIS1 gene – had previously been diagnosed with failure to thrive and delayed development, and were found to have small brain sizes. A third, who had three copies of the gene, was mentally retarded and suffered from bone deformation as well.
Reiner: “Several brain diseases, including schizophrenia, epilepsy, and autism, have been linked to faulty neuron migration, and recent research has hinted that some of these may involve variations in gene number. Our study is the first to demonstrate the effects of the duplication of a single gene in a mouse model and tie it to a new ‘copy number variation’ human disease.”
Prof. Orly Reiner’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Kekst Family Center for Medical Genetics; the David and Fela Shapell Family Center for Genetic Disorders Research; the PW-Iris Foundation; and the PW- Jani.M Research Fund. Prof. Reiner is the incumbent of the Bernstein-Mason Chair of Neurochemistry.
For the scientific paper, please see: www.nature.com/ng/journal/v41/n2/pdf/ng.302.pdf
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.
Jennifer Manning | Newswise Science News
Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine
New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
26.06.2017 | Life Sciences
26.06.2017 | Physics and Astronomy
26.06.2017 | Information Technology