New tool to track embryo's brain development in 3D

Washington: Researchers, including one of Indian-origin, have developed a new open-source software that can help track the embryonic development and movement of neuronal cells in 3D throughout the body of the worm. The tool could help better understand brain development in humans, researchers said.

Although scientists have identified a number of important proteins that determine how neurons navigate during brain formation, it is largely unknown how all of these proteins interact in a living organism. 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.

"We don't yet understand neurodevelopment even in the context of the humble worm, but we're using it as a simple model of how these factors work together to drive the development of the worm brain and neuronal structure," said Hari Shroff, head of the research team at the US National Institute of Biomedical Imaging and Bioengineering (NIBIB). "We're hoping that by doing so, some of the lessons will translate all the way up to humans," said Shroff. The team at NIBIB, in collaboration with Daniel Colon-Ramos at Yale University and Zhirong Bao at Memorial Sloan-Kettering Institute in US, developed new microscopes that improved the speed and resolution, allowing them to 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.

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, the researchers said. 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 is folded up. 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 programme, 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 programme also enables a user to check the accuracy of the computer model and edit it if any mistakes are discovered. "In addition, users can also mark cells or structures within the worm embryo they want the programme to track, allowing the users to follow the position of a cell as it moves and grows in the developing embryo," Ryan Christensen, a postdoctoral fellow at NIBIB, who led the project.

"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," said Christensen. The research was published in the journal eLife.