Studying Cell Migration With A Brain-On-A-Chip

Scientists have developed a platform that allowed them to better understand how chemical gradients induce neuron migration.

AsianScientist (Nov. 23, 2018) – In a study published in Nature Communications, a team of scientists in Hong Kong has developed a three-dimensional (3D) neuronal cultural platform to gain insights into brain development.

Neuronal migration is regulated by the graded distribution of guidance molecules. Such chemical-guided movement is known as chemotaxis. It is well known that concentration gradients of guidance molecules such as netrin or semaphorin proteins play critical roles in embryonic neural development. Yet, the interplay of gradient steepness and neuronal migration has remained unclear.

In the present study, a research team led by Associate Professor Shi Peng of the City University of Hong Kong has devised a high-throughput 3D chemotactic assay that allows scientists to track chemotaxis in vitro.

The hydrogel-based microfluidic platform is one centimeter wide and three centimeters long, and can house hundreds of suspended microscale hydrogel cylinders, each containing a distinct gradient profile to allow 3D growth of neuronal cells in an environment closely resembling the inside of developing brains.

“The major advantage of the setup is its high throughput, which allows a large collection of molecular gradient profiles to be tested in parallel using a single chip, generating a huge amount of data. Experiment times can also be reduced from months to 48 hours,” said Shi.

Using their platform and statistical analysis, the team revealed dramatic diversity and complexity in the chemotactic regulation of neuronal development by various guidance molecules. In particular, the researchers identified two signaling pathways—STK11 and GSK3—that play a significant role in coordinating neuronal migration.

“In case of brain injury, the nervous system does not regenerate easily, so the proper use of guidance molecules would help the brain recover. In this regard, our research provides insights to the development of novel therapeutic strategies,” Shi concluded.

The article can be found at: Xu et al. (2018) High-throughput Three-dimensional Chemotactic Assays Reveal Steepness-dependent Complexity in Neuronal Sensation to Molecular Gradients.


Source: City University of Hong Kong.
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