Embrio tikus dengan otak yang besar : otak berkembang lebih besar dengan DNA manusia--T-REc-komunitas reptil-semarang--KSE-komunitas satwa eksotik

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Embrio tikus dengan otak  yang besar : otak berkembang  lebih besar dengan DNA manusia

Otak manusia berkembang secara dramatis dalam ukuran selama evolusi , memberikan kita  kemampuan yang unik . Para ilmuwan sekarang telah menunjukkan bahwa hal itu mungkin untuk memilih perubahan kunci dalam kode genetik antara simpanse dan manusia dan memvisualisasikan kontribusi masing-masing untuk perkembangan otak awal embrio tikus . Temuan dapat meminjamkan wawasan apa yang membuat istimewa otak manusia dan mengapa orang mendapatkan beberapa gangguan neurologis , seperti autisme dan penyakit Alzheimer , sedangkan simpanse tidak....read more

Mouse embryo
with big brain: Evolving a bigger brain with human DNA

Date:

February 19, 2015

Source:

Duke University

Summary:

The human brain
expanded dramatically in size during evolution, imparting us with unique
capabilities. Scientists have now shown that it's possible to pick out key
changes in the genetic code between chimpanzees and humans and visualize their
respective contributions to early brain development in mouse embryos. The
findings may lend insight what makes the human brain special and why people get
some neurological disorders, such as autism and Alzheimer's disease, whereas
chimpanzees don't.

.....................

the size of the human
brain expanded dramatically during the course of evolution, imparting us with
unique capabilities to use abstract language and do complex math. But how did
the human brain get larger than that of our closest living relative, the chimpanzee,
if almost all of our genes are the same?

Duke scientists have shown that it's possible to pick out key changes in
the genetic code between chimpanzees and humans and then visualize their
respective contributions to early brain development by using mouse embryos.

The team found that humans are equipped with tiny differences in a
particular regulator of gene activity, dubbed HARE5, that when introduced into
a mouse embryo, led to a 12% bigger brain than in the embryos treated with the
HARE5 sequence from chimpanzees.

The findings, appearing online Feb. 19, 2015, in Current Biology,
may lend insight into not only what makes the human brain special but also why
people get some diseases, such as autism and Alzheimer's disease, whereas
chimpanzees don't.

"I think we've just scratched the surface, in terms of what we can
gain from this sort of study," said Debra Silver, an assistant professor
of molecular genetics and microbiology in the Duke University Medical School.
"There are some other really compelling candidates that we found that may
also lead us to a better understanding of the uniqueness of the human
brain."

Every genome contains many thousands of short bits of DNA called
'enhancers,' whose role is to control the activity of genes. Some of these are
unique to humans. Some are active in specific tissues. But none of the
human-specific enhancers previously had been shown to influence brain anatomy
directly.

In the new study, researchers mined databases of genomic data from humans
and chimpanzees, to find enhancers expressed primarily in the brain tissue and
early in development. They prioritized enhancers that differed markedly between
the two species.

The group's initial screen turned up 106 candidates, six of them near genes
that are believed to be involved in brain development. The group named these
'human-accelerated regulatory enhancers,' HARE1 through HARE6.

The strongest candidate was HARE5 for its chromosomal location near a gene
called Frizzled 8, which is part of a well-known molecular pathway implicated
in brain development and disease. The group decided to focus on HARE5 and then
showed that it was likely to be an enhancer for Frizzled8 because the two DNA
sequences made physical contact in brain tissue.

The human HARE5 and the chimpanzee HARE5 sequences differ by only 16
letters in their genetic code. Yet, in mouse embryos the researchers found that
the human enhancer was active earlier in development and more active in general
than the chimpanzee enhancer.

"What's really exciting about this was that the activity differences
were detected at a critical time in brain development: when neural progenitor
cells are proliferating and expanding in number, just prior to producing
neurons," Silver said.

The researchers found that in the mouse embryos equipped with Frizzled8
under control of human HARE5, progenitor cells destined to become neurons
proliferated faster compared with the chimp HARE5 mice, ultimately leading to
more neurons.

As the mouse embryos neared the end of gestation, their brain size differences
became noticeable to the naked eye. Graduate student Lomax Boyd started
dissecting the brains and looking at them under a microscope.

"After he started taking pictures, we took a ruler to the monitor.
Although we were blind to what the genotype was, we started noticing a
trend," Silver said.

All told, human HARE5 mice had brains 12% larger in area compared with
chimpanzee HARE5 mice. The neocortex, involved in higher-level function such as
language and reasoning, was the region of the brain affected.

Producing a short list of strong candidates was in itself a feat,
accomplished by applying the right filters to analysis of human and chimpanzee
genomes, said co-author Gregory Wray, professor of biology and director of the
Duke Center for Genomic and Computational Biology.

"Many others have tried this and failed," Wray said. "We've
known other people who have looked at genes involved in brain size evolution,
tested them out and done the same kinds of experiments we've done and come up
dry."

The Duke team plans to study the human HARE5 and chimp HARE5 mice into
adulthood, for possible differences in brain structure and behavior. The group
also hopes to explore the role of the other HARE sequences in brain
development.

"What we found is a piece of the genetic basis for why we have a
bigger brain," Wray said. "It really shows in sharp relief just how
complicated those changes must have been. This is probably only one piece -- a
little piece."

The work was supported by a research incubator grant from the Duke
Institute for Brain Sciences, the National Institutes of Health (R01NS083897),
and National Science Foundation (HOMIND BCS-08-27552).







Story Source:

The above story is based on materials provided by Duke
University. Note: Materials may be edited for content and length.







Journal Reference:

1.    J. Lomax Boyd, Stephanie L.
Skove, Jeremy P. Rouanet, Louis-Jan Pilaz, Tristan Bepler, Raluca Gordân,
Gregory A. Wray, Debra L. Silver. Human-Chimpanzee
Differences in a FZD8 Enhancer Alter Cell-Cycle Dynamics in the Developing
Neocortex. Current Biology, 2015; DOI: 10.1016/j.cub.2015.01.041

http://www.sciencedaily.com/releases/2015/02/150219133104.htm

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