Repressor Protein Blocks Neural Stem Cell Development
ScienceDaily (Oct. 12, 2007) — A protein known to repress gene
transcription at the molecular level in a variety of processes also
blocks embryonic neural stem cells from differentiating into neurons,
according to a study by University of California, San Diego and
Howard Hughes Medical Institute (HHMI) researchers published online
October 10 in Nature.
The research team focused on a repressor protein called SMRT
(silencing mediator of retinoic acid and thyroid hormone receptor),
which has been shown to repress gene expression in a number of
molecular pathways. By creating a strain of "knock-out" mice missing
the SMRT gene, the team was able to pinpoint significant alterations
in brain development in the absence of SMRT. These findings
demonstrate the important role of this protein in preventing
premature differentiation of specific brain cells from
undifferentiated neural stem cells in utero.
"By showing that SMRT prevents differentiation by maintaining neural
stem cells in a basic stem cell state, we now have a target to study
further how stem cells restrict themselves from differentiating,
said first author Kristen Jepsen, Ph.D., an assistant research
scientist at the UC San Diego School of Medicine.
The research team also noted that in the SMRT-deficient mice, the
brain exhibited signs of excessive exposure to retinoic acid--
naturally occurring vitamin A--which is a known teratogen (an agent
which causes birth defects). This finding suggests that in addition
to maintaining neural stem cells in a pre-differentiated state, the
SMRT protein controls retinoic-acid induced differentiation and, when
missing, abnormalities that mimic vitamin A exposure occur.
This finding provides scientists with one more important key to
understanding how stem cells maintain their potential to grow into
specific cells.
"Incremental steps such as this lay the groundwork for continuing
studies investigating the potential of stem cells to be used
therapeutically to replace damaged or deficient cells associated with
disease," said Jepsen.
Co-authors of the Nature paper are Derek Solum, Ph.D., Tianyuan Zhou,
Ph.D., Robert McEvilly, Ph.D. and Hyun-Jung Kim, Ph.D., of HHMI and
UC San Diego; Christopher Glass, M.D., Ph.D., professor of cellular
and molecular medicine at UC San Diego; Ola Hermanson, Ph.D. of the
Karolinska Institutet in Sweden, and senior author Michael G.
Rosenfeld, M.D., HHMI investigator and professor of medicine at UC
San Diego.
Adapted from materials provided by University of California - San
Diego.
http://www.scienced
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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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