“This is the first systematic mapping of all of the major brain areas
that shows what regulatory genes are expressed in those specific
locations,?said Quifu Ma, PhD, of Dana-Farber’s Cancer Biology
Department. He is senior author of a paper appearing in today’s online
issue of the journal Science, along with Charles D. Stiles, PhD, also
Transcription factors are genes that control the expression, or
activity, of “target?genes. These factors play a pivotal role in brain
development by direction the formation of neurons and supporting cells
called glia from uncommitted progenitor cells. Until now, brain
transcription factors had not been systematically isolated and their
locations within different parts of the brain pinned down.
The map should tell scientists studying different parts of the brain,
which transcription factor (TF) genes regulate the development of that
brain region, and which of them to investigate as possible causes of
brain tumors and other diseases.
The Dana-Farber researchers already have homed in on specific TF genes
regulating nerves involved in pain sensation, certain brain tumors, and
speech problems caused by abnormally developing motor neurons that
control muscles of the tongue.
The map, known as the Mahoney Transcription Factor Atlas, has been
ced online where it is freely accessible to researchers studying
brain development and disorders.
To compile the atlas, the investigators first sifted through databases
of information from the Human Genome Project, singling out all genes in
the mouse that appeared to be transcription factors: they turned up
1,445 of them. Next, they determined that more than 1,000 of these TF’s
were expressed in the brains of developing mice.
Using genetic probes to investigate thin sections of mouse brains, the
scientists found that only 349 of the TF genes were expressed in
specific regions, and not throughout the brain, as the majority were.
They inferred that these 349 genes, therefore, controlled the
development of the particular areas or structures in which they were
Stiles is pursuing TF’s that direct the formation of astrocytes, which
are affected in tumors called gliomas. David Rowitch, MD, PhD, of
Dana-Farber and an author on the paper, studies transcription factors
in the brain’s cerebellum, where tumors called medulloblastomas occur,
and Ma has identified TF’s that regulate the nerves involved in the
sensation of specific types of pain. Ma’s laboratory is focused on the
stubborn problem of cancer pain: He and his students are screening the
atlas for transcription factors that regulate development of the
neurons that generate the severe pain that is a common symptom of
The research was funded by the Charles Dana Foundation, the National
Institutes of Health, and individual fellowships.
Dana-Farber Cancer Institute is a principal teaching affiliate of the
Harvard Medical School and is among the leading cancer research and
care centers in the United States. It is a founding member of the
Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive
cancer center by the National Cancer Institute.
Source:Dana-Farber Cancer Institute
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