Mixing and matching genes to keep nerve cells straight

June 9, 2008

With fewer than 30,000 human genes with which to work, Nature has to mix and match to generate the myriad types of neurons or nerve cells needed to assemble the brain and nervous system. Keeping this involved process on the straight and narrow requires a clever balance of promotion and inhibition, said researchers from Baylor College of Medicine in Houston in a report that appears in the current edition of the journal Developmental Cell.

"Our finding should have implications for the entire stem cell field," said Dr. Soo-Kyung Lee, assistant professor of molecular and cellular biology at BCM. "Scientists are seeking to make particular cell types using combinations of embryonic genes. They need to keeping mind that you do not just push them forward down one pathway. You must also suppress related pathways."

"During embryonic development, one needs to generate a lot of different types of neurons," said Lee, also a faculty member in the BCM Graduate School of Biomedical Sciences. "How are they being generated at the right time and place? To assemble the brain, you need all these different types of neurons. With a limited number of genes, how do you generate such a complex system?"

"We want to understand the molecular mechanisms that allow one gene to influence the formation of many neurons," she said.

They found that both promotion of one pathway and inhibition of another are required to keep the cells on the right road to cell fate determination.

"One factor does not determine cell fate," she said. It's a combination of factors or genes that together affect neuron formation.

She and her colleagues concentrated their work on the development of motor neurons in mice. Two types of nerve cells – spinal motor neurons and V2-interneurons – are required for motor coordination. As they become those cells, they share important regulatory factors, said Lee.

"They share a cell lineage pathway," she said. "We asked how do we generate two different lineages from one pathway?"

A cocktail of the transcription factors Isl1 and Lhx3 can cause embryonic cells to become motor neurons, she said.

"If we put only Lhx3 into the embryonic neural stem cells, they become V2-interneurons," she said. However, deleting the genes can cause the pathways to converge, resulting in hybrid cells that result in the death of the embryos.

This does not happen in Nature, she said, and they found that a gene called Hb9, expressed only in motor neurons, blocks the ability of Lhx3 to cause embryonic neural stem cells to become the V2-interneurons.

"Once you turn on the complex of Isl1 and Lhx3, then you also turn on a repressor that blocks the cells from going down the alternative pathway to becoming V2-interneurons," she said. The motor neuron fate of those cells is sealed. They found a similar repressor function in the V2-interneuron pathway.

"We think this is a delicately developed system," said Lee. "We don't think this mechanism is restricted to motor neurons."

Source: Baylor College of Medicine

Explore further: Swinging on 'monkey bars': Motor proteins caught in the act

Related Stories

Biologists find keys to driving a cockroach

October 22, 2015

Researchers at Case Western Reserve University have identified neurons in a cockroach's brain that control whether the insect walks slow or fast, turns right or left or downshifts to climb.

Signal replicas make a flexible sensor

September 4, 2015

Ludwig Maximilian University of Munich researchers have shown how signals from the spinal cord adjust the sensitivity of hair cells in the inner ear to accommodate shifts in head position associated with active locomotion—thus ...

From skin cells to motor neurons

August 29, 2011

A team of Harvard stem cell researchers has succeeded in reprogramming adult mouse skin cells directly into the type of motor neurons damaged in amyotrophic lateral sclerosis (ALS), best known as Lou Gehrig’s disease, ...

Preserving nerve cells in motor neuron disease

September 20, 2010

A team of researchers, led by Scott Oakes, at the University of California, San Francisco, has identified a way to prevent symptom onset, weight loss, and paralysis and extend survival in a mouse model of amyotrophic lateral ...

Recommended for you

'Material universe' yields surprising new particle

November 25, 2015

An international team of researchers has predicted the existence of a new type of particle called the type-II Weyl fermion in metallic materials. When subjected to a magnetic field, the materials containing the particle act ...

CERN collides heavy nuclei at new record high energy

November 25, 2015

The world's most powerful accelerator, the 27 km long Large Hadron Collider (LHC) operating at CERN in Geneva established collisions between lead nuclei, this morning, at the highest energies ever. The LHC has been colliding ...

New gene map reveals cancer's Achilles heel

November 25, 2015

Scientists have mapped out the genes that keep our cells alive, creating a long-awaited foothold for understanding how our genome works and which genes are crucial in disease like cancer.

A blue, neptune-size exoplanet around a red dwarf star

November 25, 2015

A team of astronomers have used the LCOGT network to detect light scattered by tiny particles (called Rayleigh scattering), through the atmosphere of a Neptune-size transiting exoplanet. This suggests a blue sky on this world ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.