Cerebral sensory development: Genetic programming versus environmental stimuli

Dec. 22, 2013 — Hiroshi Kawasaki and colleagues at Kanazawa University, Tokyo University, Tokyo Institute of Technology and Kumamoto University in Japan have identified how sensory map development is regulated in mice pups at birth, and the molecular signalling responsible.

The part of the brain associated with the sense of touch -- the somatosensory cerebral cortex -- has attracted numerous studies aimed at determining the influence of extrinsic environmental and intrinsic genetic factors in sensory development. Understanding the role of these factors in sensory map formation and development may provide insights into the mechanisms behind other circuits in the central nervous system.

Now Hiroshi Kawasaki and colleagues at Kanazawa University, Tokyo University, Tokyo Institute of Technology and Kumamoto University in Japan have identified how sensory map development is regulated in mice pups at birth, and the molecular signalling responsible.

Rodents have a sensory map in the primary somatosensory cerebral cortex, characterized by cell clusters called barrels filled with patches of nerve fibre. Inputs from the part of the brain that link to the rodent's whiskers terminate at these barrels. The barrel distribution pattern is the same as the distribution of the whiskers on the snout and forms soon after birth.

The researchers induced preterm birth in mice and quantitatively compared the degree of development of whisker-related barrel pattern formation with mice born after the full term of pregnancy. At set periods after conception, barrel formation was significantly more advanced in the mice born preterm. Further experiments ruled out the role of maternal hormones prior to birth and identified the critical effect of serotonin reductions during the days after birth.

"Interestingly, the regulatory mechanisms described here were also found to regulate eye-specific segregation in the visual system, raising the possibility that they are utilized in various brain regions," the researchers suggest. They add that further investigation of the range of roles of serotonin and the underlying mechanisms will be interesting for future research.

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The above story is based on materials provided by Organization of Frontier Science and Innovation, Kanazawa University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Tomohisa Toda, Daigo Homma, Hirofumi Tokuoka, Itaru Hayakawa, Yukihiko Sugimoto, Hiroshi Ichinose, Hiroshi Kawasaki. Birth Regulates the Initiation of Sensory Map Formation through Serotonin Signaling. Developmental Cell, 2013; 27 (1): 32 DOI: 10.1016/j.devcel.2013.09.002

Note: If no author is given, the source is cited instead.

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Common genetic pathway can be a conduit to the Pediatric Oncology treatment

Johns Hopkins and Kimmel Cancer Center investigators provide new target for the treatment of these cancers may, discovered the genetic pathway is known in many difficult to treat pediatric brain tumor called a low-grade glioma. The pathway is called the mammalian target of rapamycin in laboratory studies researchers found (mTOR) Pediatric low-grade glioma tumors are very active and, using an experimental drug may block mTOR activity these decreased growth.

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By the genetic effects of sharing new approaches subtypes cancers

Develop a fact that tumors are almost never confounded the shared scientific efforts with exactly the same genetic mutation, cancer types targeted more predicaments, effective treatment. Paper published in the online edition of nature methods and advanced 9/15 California College San Diego (Moores Comprehensive Cancer Center home ） of researcher presents a new approach called network-based stratified (NBS) to identify subtypes of cancer due to shared genetic networks and systems of these mutations, not peculiar mutation in each patient.

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New technique in RNA interference cuts time and cost in genetic screens

Sep. 13, 2013 — There is a new contender in the field of gene discovery, and it's giving knockout mice a run for their money. Researchers at The Rockefeller University have shown that a new technique using RNA interference is able to find genes that cause epidermal tumor growth in months rather than the decades it may take using traditional methods employing specially bred, genetically altered mice. They recently revealed the first genome-wide RNA interference screen of a mouse in an article published in Nature.

RNA interference is a natural process by which RNA molecules inhibit gene expression, but it can also be used by scientists to block a gene's function and look for those that contribute to certain diseases.

"For years, fruit flies and worms have been great model organisms because of the ability to carry out rapid genetic screens," says Elaine Fuchs, Rebecca C. Lancefield Professor. "Genetic screens in mammalian cells have been limited to petri dishes, where cells are exposed to stress and nonphysiological growth conditions."

Doing the screen involves using short pieces of RNA, called small hairpin RNAs, which are inserted into the cell and are able to halt messages from specific genes, keeping the genes from making proteins. A genetic screen might look at 15,000 genes -- meaning thousands of petri dishes or fruit flies -- a task deemed far too large, time-consuming and costly to do with current mouse knockout technology. But researchers led by Slobodan Beronja, a former postdoc in Fuchs's Laboratory of Mammalian Cell Biology and Development, created a special method of RNA interference, where the small hairpin RNAs are all pooled together and injected into the embryos of pregnant mice using a virus.

"We've now devised a technology where we can effectively treat the surface of living mouse embryos as a petri dish of cells, and carry out genome wide screens on mouse cells in their native environment in vivo," says Fuchs. "Previously, genome-wide screens were only possible in lower animals, such as flies, worms and yeast, where it is often difficult to assess the relevance to human disorders such as cancer."

After allowing for normal or pre-cancerous tissues to grow, the researchers quantified the number of individual small hairpin RNAs in the animals, and used it as a measure of their relative importance to the growth process, Beronja, now an assistant member at the Fred Hutchinson Cancer Research Center, explains. The result is the ability to screen more genes with fewer mice. The team screened over 16,000 genes using just 100 litters of mice, and identified about 200 genes that were uniquely important to oncogenic growth in the skin.

"We wanted to identify new genes that are worthy of creating drugs against in cancer treatment," says Beronja. "The greater the complexity of the drug treatment, the greater its success. If you attack several genes, it's more effective."

The researchers found several genes that were already known to cause tumor growth, but many, including one known as Mllt6, surprised them. Although there has been some research on it in leukemia, the gene had never been linked to solid tumors.

"The next step is to validate the list of 200-plus genes and narrow it down to the true candidates for drug therapy. Mllt6 is one that needs further exploration," says Beronja. "But we have shown that this method of genetic screening is cheaper, easier and more informative. It was a risky undertaking that Dr. Fuchs entrusted me to take, and it paid off."

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Reveals the genetic causes of childhood leukemia.

For the first time, a genetic link specific childhood leukemia risk has been identified, according to the team of researchers from the Memorial Sloan-Kettering Cancer Center, St. Jude children's research hospital and Washington University （ affiliate Fred Hutchinson Cancer Research Center ）, and other institutions. Discovery is reported in the online journal Nature Genetics.

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Among the research institutions in NCI funding, all over the United States that current cancer specifies 68 as a Center. Based at research universities, these facilities are cancer's origin and development of intense laboratory research wide range, the scientists from NCI support many home. Cancer Center program is also focused on cross-cutting research, population Sciences, and clinical research please. Center for research results are often at the forefront of cancer research.

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