Mixing and matching genes to keep nerve cells straight
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,
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,
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
http://www.physorg.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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