‘Simple, But Powerful’ Model Reveals Mechanisms Behind Neuron Development

Source: The Scripps Research Institute

Summary: Researchers have uncovered new insights into the regulatory network of the controlled termination of individual neuron growth, especially the extensions – axons.

Everything must come to an end and is particularly true for neurons, especially the axon part which transmit electrochemical signals to other neurons. Axons are long cellular structures that project outward from the neuron body. Over the course of their development, axons extend, change their growth in response to cellular guidance cues and form synapses. There is a specialized structure on the end of each axon called a growth cone. Successful development depends on the growth cone stopping at the correct destination and when the axon reaches the correct length by a process known as axon termination. With the only controlled termination of individual neuron growth, the construction of the nervous system is efficient and accurate. Researchers from the Scripps Research Institute have uncovered new insights into the regulatory network behind this controlled termination. The research findings were published in the journal Development.

Neuron development depends of axon termination process

Credit: CC0 Public Domain

C.elegans(nematode) was used as a model for this study. Researchers for the first time found that growth cone collapse prior to axon termination is protracted as the growth cone transitions from a dynamic to a static state. What they found in their simple but powerful model was that a signaling hub protein called RPM-1 is required to regulate the collapse of growth cones during axon termination. It’s the protracted nature of the process that is likely to make the transition and the termination permanent. The study also showed some surprising results that RPM-1 signaling destabilizes nerve axon microtubules, the microtubule stabilizer Tau potentially inhibits RPM -1, something that was previously unknown. The research has implications for the development of neurological disorders.

Assoc. Prof. Brock Grill said, “You wouldn’t necessarily have thought Tau and RPM-1 would function this way”, “That’s the power of genetics. Although we assessed the genetic relationship between Tau and RPM-1 in axon development, our results could have important implications for neurodegeneration.”

More Information: Melissa A. Borgen et al, “RPM-1 Regulates Axon Termination by Affecting Growth Cone Collapse and Microtubule Stability,” Development (2017). doi: 10.1242/dev.154187

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