NIH 3-D software tracks worm embryo’s brain development
A new, open-source software that can help track the embryonic development and movement of neuronal cells throughout the body of the worm, is now available to scientists. The software is described in a paper published in the open access journal, eLife on December 3rd by researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Center for Information Technology (CIT); along with Memorial Sloan-Kettering Institute, New York City; Yale University, New Haven, Connecticut; Zhejiang University, China; and the University of Connecticut Health Center, Farmington. NIBIB is part of the National Institutes of Health.
Although scientists have identified a number of important proteins that determine how neurons navigate during brain formation, it’s largely unknown how all of these proteins interact in a living organism. Model animals, despite their differences from humans, have already revealed much about human physiology because they are much simpler and easier to understand. In this case, researchers chose Caenorhabditis elegans (C. elegans), because it has only 302 neurons, 222 of which form while the worm is still an embryo. While some of these neurons go to the worm nerve ring (brain) they also spread along the ventral nerve cord, which is broadly analogous to the spinal cord in humans. The worm even has its own versions of many of the same proteins used to direct brain formation in more complex organisms such as flies, mice, or humans.
However, following neurons as they travel through the worm during its embryonic development is not as simple as it might seem. The first challenge was to create new microscopes that could record the embryogenesis of these worms without damaging them through too much light exposure while still getting the resolution needed to clearly see individual cells. Shroff and his team at NIBIB, in collaboration with Daniel Colon-Ramos at Yale University and Zhirong Bao at Sloan-Kettering, tackled this problem by developing new microscopes that improved the speed and resolution at which they could image worm embryonic development. (Read more)
The second problem was that during development the worm begins to “twitch”, moving around inside the egg.
The folding and twisting makes it hard to track cells and parse out movement. For example, if a neuron moves in the span of a couple of minutes, is it because the embryo twisted or because the neuron actually changed position within the embryo? Understanding the mechanisms that move neurons to their final destination is an important factor in understanding how brains form—and is difficult to determine without knowing where and how a neuron is moving. Finally, it can be challenging to determine where a neuron is in 3D space while looking at a two-dimensional image—especially of a worm that’s folded up.
The worm embryo is normally transparent, but the researchers made several cells in the embryo glow with fluorescent proteins to act as markers. When a microscopic image of these cells is fed into the program, the computer identifies each cell and uses the information to create a model of the worm, which it then computationally “untwists” to generate a straightened image. The program also enables a user to check the accuracy of the computer model and edit it when any mistakes are discovered.
In addition, users can also mark cells or structures within the worm embryo they want the program to track, allowing the users to follow the position of a cell as it moves and grows in the developing embryo. This feature could help scientists understand how certain cells develop into neurons, as opposed to other types of cells, and what factors influence the development of the brain and neuronal structure.
NIBIB’s mission is to improve health by leading the development and accelerating the application of biomedical technologies. The Institute is committed to integrating the physical and engineering sciences with the life sciences to advance basic research and medical care. NIBIB supports emerging technology research and development within its internal laboratories and through grants, collaborations, and training. More information is available at the NIBIB website: http://www.nibib.nih.gov.
The National Institutes of Health, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.