Genome complexity: how neurons grow their axons (Introduction)

by David Turell , Monday, February 04, 2019, 17:52 (1909 days ago) @ David Turell

An axon carries electrical signals from the body of the neuron. The neuron is the only cell that has an enormous extension,think from your lower back to a toe:

https://medicalxpress.com/news/2019-02-neural-heaven-neuron-axon.html

"In a new paper, a researcher at the University of California, Riverside, and his colleagues describe the genetic switches that ignite axon formation. Their work focuses on two molecular components—polypyrimidine tract binding protein 2 (PTBP2) and the shootin gene (SHTN1).

"'Neurons are so distinct from other cells in the body," said Sika Zheng, assistant professor of biomedical sciences in the School of Medicine at the University of California, Riverside. "They are the only cells that can grow a protrusion (the axon) that can become hundreds and thousands of times longer than the cell body itself."

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"Previous studies have identified more than 150 genes that play some roles in axon function. Zheng and his team were surprised to find the overall expression levels of these genes stay relatively flat as the axon grows. If these genes do not change their abundance, how then do they dictate neurons to produce axons?

"These genes do change their "character" through a gene regulatory process called alternative splicing. Alternative splicing allows a single gene to produce multiple similar protein isoforms with different functions or identities. According to Zheng, it is as if these genes are transformed to shoulder a new task—in this case generating an axon.

"PTBP2, a specialized RNA binding protein, was about to take center stage in the study. Zheng and his team found PTBP2 spiked in immature neuron cells. This protein orchestrates the precise choreography behind those splicing events by acting like a switchboard controlling every step of the process that produces the one, essential axon.

"At the early stage of axon formation, PTBP2 turns on the long isoform of the SHTN1 gene, which promotes growth of the axon. As the neuron matures, PTBP2 is gradually down regulated and the SHTN1 gene switches from the long isoform to the short isoform. Axon growth stops as the neuron and its axon connect to the neural circuit.

"'PTBP2 and SHTN1 give us an entry point to understand how splicing changes occur to promote axon growth," Zheng said. "We can use this information to tease out what is happening at the cellular level, and we are only at the tip of the iceberg."

"While this study focused on PTBP2 and the SHTN1 gene, Zheng notes that other proteins or genes and their isoforms could also play a role in axon formation. This study was also conducted using mouse neural cells. Zheng and his team do not know if the same mechanisms will be active in human neural cells. While the study offers a new perspective to this fundamental question, Zheng cautions that it may be years before these findings could be translated into future therapies."

Comment: Once again we see the complex controls and the resulting axon formation, but we have no information about how it all works, or how the cell and the cells genes manipulate each other. The inner workings are all a black box. We do not know whether all of this is automatic, or alternatively there must be some independent initiation activity