Investigators at St. Jude Children's Research Hospital have discovered in mouse models that a gene called Six3 is one of the earliest critical regulators controlling lens development in the eye of the mammalian embryo.
Mutations in Six3 have been previously identified in patients with holoprosencephaly, a disease that can cause the part of the brain called the cerebrum to fail to divide normally into two lobes. Holoprosencephaly is the most common abnormality of the development of the forebrain (front part of the brain) in humans. A few years ago the St. Jude team demonstrated that Six3 activity is critical for the normal development of the forebrain in mice.
St. Jude researchers have now extended these results by showing in the developing eye that Six3 normally exerts its effect by directly activating Pax6, a gene considered the "master regulator of eye development." In the absence of Six3, Pax6 fails to coordinate the activity of a series of additional genes that cooperate to form the lens. A report on this work appears in the prepublication online issue of The EMBO Journal.
Previously, the researchers were not able to address the gene's possible role in mouse eye formation because inactivation of Six3 significantly disrupted development of the area of the brain where the eye normally forms. The St. Jude team overcame this problem by taking advantage of Cre/loxP-technology, which allowed them to choose the time and place in which to remove Six3 function from specific cells. This permitted the investigators to remove Six3 activity from the presumptive lens ectoderm (PLE)--the area of the developing head where the lens will ultimately form in response to a series of biochemical signals. Following this systematic approach, the St. Jude team demonstrated that Six3 plays its important role in the PLE. The investigators also showed that a key consequence of removing Six3 during early development is that the PLE fails to undergo its normal thickening, an initial critical step in lens formation.
"Our discovery helps to better unravel the regulatory pathway that controls normal lens formation," said the paper's senior author, Guillermo Oliver, Ph.D., a member of the St. Jude Genetics and Tumor Cell Biology department. "Specifically, it puts the Six3 gene at the top of the genetic cascade that controls the development of the lens. Understanding the early steps leading to lens formation will help us determine what goes wrong in disorders in which the lens does not form, or forms abnormally. That kind of information is often the first step in designing both preventive and treatment strategies for congenital diseases."
The St. Jude team further showed that the proteins coded for by Six3 are present in the PLE before those coded by Pax6. This was evidence that production of Pax6 proteins in that region of the head starts after Six3 proteins are made, further supporting the idea that the Six3 gene controls the Pax6 gene. The researchers also demonstrated that the Six3 protein directly controls the expression of the Pax6 gene by binding to some of the DNA regions that regulate Pax6 activity.
"Our work confirms the early and vital role Six3 plays in the overall development of the eye, and gives us important insights into the interplay of genes during this time," said Wei Liu, Ph.D., a postdoctoral fellow in Oliver's laboratory. Lui is first author of the paper.
Carrie Strehlau | EurekAlert!
Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg
The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision
Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...
19.07.2017 | Event News
12.07.2017 | Event News
12.07.2017 | Event News
20.07.2017 | Information Technology
20.07.2017 | Materials Sciences
20.07.2017 | Physics and Astronomy