Building Brains By Modifying Protein Signals

From: J. R. Molloy (
Date: Fri Sep 21 2001 - 11:37:08 MDT

A new model of cerebral cortex development

For the first time, University of Chicago researchers, using a newly developed
technique, report that a molecular mechanism involved in formation of limbs
other body structures is also used to organize the higher functions of the

Specific brain functions, such as vision, touch and memory, are set out in a
pattern of distinct areas in the outer layer of the brain, the cerebral
Because these areas can only be seen after birth, it has been impossible until
now to determine the molecular mechanisms responsible for forming them in the

"We knew that signaling proteins associated with patterning other parts of the
body found in the embryo cortex, but we did not have an easy way to find out
what they were doing there," said Elizabeth Grove, assistant professor of
neurobiology, pharmacology and physiology at the University of Chicago and
principal investigator in the study. "There has been some speculation that
cortical patterning depended on completely unique mechanisms."

In the September 20, 2001 edition of Science Express, the researchers report
that manipulating one of these signaling proteins in the developing mouse
causes radical changes in the cortex.

Tomomi Fukuchi-Shimogori, Ph.D., research associate in neurobiology,
pharmacology and physiology at the University of Chicago, and lead author of
the paper, developed a microsurgical technique that allows her to insert genes
into the cortex of mice while they are still in utero, about halfway through
gestation. The mice are born normally and can be analyzed at any age.

Fibroblast Growth Factor 8 (FGF8), a member of a family of signaling proteins
involved in forming other structures in the embryo, is normally found near the
front of the developing cortex. Using this technique, the researchers were
to manipulate the amount and position of this signaling protein in the embryo
and look for changes in the cortical pattern much later.

The researchers increased the amount of the signaling protein in its normal
position, decreased it by inserting a gene for a receptor able to soak up the
protein, or expressed it in a new position. Each manipulation profoundly
affected cortical area pattern.

"We found very strong evidence that this signaling protein directs the
development of the cortex," said Fukuchi-Shimogori.

With increased expression of this protein the sizes and locations of the areas
changed. Areas that are towards the front of the cortex and closer to the
source of the molecule were enlarged at the expense of areas further away from
the source. Reducing the signaling protein caused shifts in the opposite

"Most dramatic, when a new source of the signaling protein was generated close
to the back of the embryonic cortex, the whole program changed," said Grove.
"Now, a region near the back of the cortex was reprogrammed to form a
of a more central region, a second touch area. We saw a identical array of
patches that correspond on a one-to-one basis with the mouse's whiskers." (see

The generation of a new cortical area by a molecular manipulation has not been
seen before and may provide a clue about how the cerebral cortex changes in
evolution. One way that evolution seems to generate more functionally complex
brains is by adding new areas to the cortex.

"We have had no idea how evolution achieved this kind of change," said Grove.
"So it is exciting to find that you can add a new area by modifying signaling
by a single protein."

This research was supported by the National Institutes of Health and the March
of Dimes Birth Defects Foundation.

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Useless hypotheses, etc.:
 consciousness, phlogiston, philosophy, vitalism, mind, free will, qualia,
analog computing, cultural relativism, GAC, Cyc, Eliza, cryonics, individual
uniqueness, ego, human values, scientific relinquishment

We won't move into a better future until we debunk religiosity, the most
regressive force now operating in society.

     Everything that can happen has already happened, not just once,
     but an infinite number of times, and will continue to do so forever.
     (Everything that can happen = more than anyone can imagine.)

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