Motor Neuron Differentiation Specified By 2 Signals -- From Within And Out Of Ce

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Motor Neuron Differentiation Specified By 2 Signals -- From Within And Out Of

Cell

http://www.medicalnewstoday.com/articles/153563.php

Two signals - an external one from retinoic acid and an internal one from the

transcription factor Neurogenin2 - cooperate to activate chromatin (the basic

material of chromosomes) and help determine that certain nerve progenitor cells

become motor neurons, said researchers from Baylor College of Medicine in a

report in the current issue of the journal Neuron.

" This finding is important for many reasons. For example, as we understand more

about what happens, the more likely we will be able to generate motor neurons

from different types of stem cells, " said Dr. Soo-Kyung Lee, assistant professor

of molecular and human genetics and molecular and cellular biology at BCM. (A

motor neuron conducts impulses from the spinal cord to a muscle fiber,

controlling movement and other activities.) " It will also be useful as a tool

for drug screening, allowing us to determine whether a drug is killing or

enhancing the activity of motor neurons. "

In a delicate series of experiments, she and her colleagues showed that a

complex consisting of Neurogenin2 and the retinoic acid receptor, when bound to

retinoic acid, recruit a particular enzyme (histone acetyltransferase CBP) to

their complex. This causes a chemical reaction called acetylation of the

histones (the spools around which DNA winds in the chromatin), stimulating the

transcription of the gene into the protein for which it holds the genetic code.

" These changes lead to strong expression of the motor neuron genes in nerve

progenitor cells, converting them to motor neurons, " said Lee. " What is striking

is that the retinoic acid receptor uses the Neurogenin2 site to bind to the

DNA. "

In mice that lack CBP, she said, there is marked reduction in motor neurons. The

finding could play a role in unraveling the secrets of diseases such as the

muscular dystrophies.

Notes:

This work was spearheaded by Dr. Seunghee Lee. Others who also took part in this

study are Drs. Bora Lee and Jae W. Lee, all of BCM.

Funding for this work came from the National Institute of Neurological Disorders

and Stroke, the PEW Trust, the March of Dimes Foundation and the Intellectual

and Developmental Disability Research Centers.