PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Scripps Research Institute scientists find key signal that guides brain development

2013-08-07
(Press-News.org) LA JOLLA, CA – August 7, 2013 – Scientists at The Scripps Research Institute (TSRI) have decoded an important molecular signal that guides the development of a key region of the brain known as the neocortex. The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans and is responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness and other functions.

"The mammalian neocortex has a distinctive structure featuring six layers of neurons, and our finding helps explain how this layered structure is generated in early life," said Ulrich Mueller, chair of TSRI's Department of Molecular and Cellular Neuroscience and director of the Dorris Neuroscience Center at TSRI.

The discovery, which appears in the August 7, 2013 issue of Neuron, also is likely to aid research on autism, schizophrenia and other psychiatric conditions. "With studies such as this one, we're starting to understand the normal functions of molecules whose disruption by gene mutations can cause developmental brain disorders," Mueller said.

Finding Their Proper Place

The signal uncovered by Mueller's team is one that helps guide the migration of baby neurons through the developing neocortex. Such neurons are born from stem-like cells at the bottom of the neocortex, where it wraps around a large, fluid-filled space in the brain called ventricle. The newborn neurons then migrate upward, or radially away from the ventricle, being directed to their proper places in the neocortex's six-layered, columnar structure by—among others—special guide cells called Cajal-Retzius (CR) cells.

Decades ago, scientists discovered a key signaling protein, reelin, which CR cells secrete and baby neocortical neurons must detect to migrate properly. (Mutant mice that lack a functional form of the protein show, among other abnormalities, a reeling gait—thus the name.) There have been hints since then that CR cells and baby neocortical neurons exchange other molecular signals, too. "But in many years of study, no one has been able to find these other signals," said Mueller.

However, in a study published in 2011, Mueller and his laboratory colleagues found a significant clue. Reelin, they discovered, guides neuronal migration at least in part by boosting baby neurons' expression of a generic cell-adhesion molecule, cadherin2 (Cdh2). Since Cdh2 can be expressed by almost any cell type in the developing neocortex, the team then began to look for other factors that would account for the specificity of the interaction between CR cells and migrating baby neurons.

An Interesting Pattern

One set of candidates were the nectins—cell-adhesion proteins known to work with cadherins in other contexts. Lead author Cristina Gil-Sanz, a senior research associate in the Mueller laboratory, mapped the expression levels of the four known types of mammalian nectin proteins in the developing mouse cortex and found an interesting pattern. "We observed that nectin1 is expressed specifically by CR cells and nectin3 by migrating neurons," said Gil-Sanz. "At the same time, we knew from previous research that nectin1 and nectin3 are preferred binding partners."

Gil-Sanz and her colleagues followed up with other experiments and soon confirmed that the hookup of nectin1 on CR cells with nectin3 on baby neurons is essential for proper neuronal migration. "This showed for the first time the importance of direct contacts between CR cells and migrating neurons," Gil-Sanz said.

The experiments also showed that this direct nectin-to-nectin connection is effectively part of the reelin signaling pathway, since reelin's promotion of Cdh2's function in migrating neurons turns out to work largely via nectin3. "This helps explain how the interaction occurs specifically between neurons and CR cells, and doesn't involve other nearby cells that also express Cdh2," she said.

New Possibilities

The finding points to the possibility of other cell-specific pairings that work via generic Cdh2-to-Cdh2 adhesions in brain development. "We know that there are four nectin proteins, plus a slew of nectin-like molecules," said Mueller. "We think that there are others that do this as well, and we're hoping to find them."

The new study represents a big step toward the full scientific understanding of neuronal migration in the neocortex, and it is likely to be relevant to the study of developmental brain diseases too.

Reelin-signaling abnormalities in humans have been linked to autism, depression, schizophrenia and even Alzheimer's, and, in recent years, cadherin protein mutations also have been linked to disorders including schizophrenia and autism. "Studies like ours provide insight into such findings, by showing that these molecules, in cooperation with nectins, regulate key developmental processes such as the positioning of neurons in the neocortex," said Mueller.



INFORMATION:

Contributors to the study, "Cajal-Retzius cells instruct neuronal migration by coincidence signaling between secreted and contact-dependent guidance cues," included also Santos J. Franco, Isabel Martinez-Garay (now working in the Department of Physiology, Anatomy and Genetics of the University of Oxford, UK), Ana Espinosa and Sarah Harkins-Perry of TSRI.

The study was made possible by funding from the National Institutes of Health (grants NS060355, NS046456, MH078833, HD070494), the Dorris Neuroscience Center and the Skaggs Institute for Chemical Biology at TSRI, the California Institute of Regenerative Medicine, the Spanish Ministry of Education (EX2009-0416; FU-2006-1238) and Generalitat Valenciana (APOSTD/2010/064).



ELSE PRESS RELEASES FROM THIS DATE:

Psychological adaptation to urbanization, technology reflected in word usage over last 200 years

2013-08-07
New research shows that as culture has evolved over the last two centuries – with increasing urbanization, greater reliance on technology, and widespread availability of formal education – so has human psychology. The findings are forthcoming in Psychological Science, a journal of the Association for Psychological Science. "This research shows that there has been a two-century long historical shift towards individualistic psychological functioning adapted to an urban environment and away from psychological functioning adapted to a rural environment," says psychological ...

Changes in language and word use reflect our shifting values, UCLA psychologist reports

2013-08-07
A new UCLA analysis of words used in more than 1.5 million American and British books published between 1800 and 2000 shows how our cultural values have changed. The increase or decrease in the use of certain words over the past two centuries — a period marked by growing urbanization, greater reliance on technology and the widespread availability of formal education — reveals how human psychology has evolved in response to major historical shifts, said Patricia Greenfield, a distinguished professor of psychology at UCLA and the author of the study. For instance, ...

AAAS report shows steady escalation of destruction in Aleppo

2013-08-07
In Syria's largest city, Aleppo, damage to buildings and infrastructure steadily increased over a ten-month period ending in May 2013, according to a new analysis by AAAS of high-resolution satellite images. Virtually all of the destruction appears to be in rebel-controlled or contested areas, and a substantial amount is in Aleppo's Ancient City, a UNESCO World Heritage Site. Aleppo has been the site of ongoing conflict since July 2012. Since then, the city has experienced a nearly constant rate of damage to its physical structures, at about three incidents per day on ...

The team of proteins that could have implications for the fight against cancer

2013-08-07
Researchers at Warwick Medical School have identified the key role played by a team of proteins in the process of mitosis. Working out how to control them may give scientists a way to destroy cancerous cells. The study, led by Professor Steve Royle and published in The Journal of Cell Biology, highlights the role of a newly identified team of proteins, TACC3-ch-TOG-clathrin, in forming inter-microtubule bridges that stabilise the kinetochore fibres (K-fibres) used in mitosis. When a cell divides, it produces a mitotic spindle which then makes sure that the chromosomes ...

Brain activation when processing Chinese hand-radicals

2013-08-07
A number of studies in which patients with lesions to frontal pre-motor areas are included have identified deficits in action comprehension. In addition, imaging studies have revealed the activation of brain areas associated with perception or action during tasks involving reading of words with related semantic meaning. For example, the mere passive reading of action verbs such as kick, pick and lick has been found to activate areas of the sensory-motor cortex associated with the legs, hands and face, respectively. To investigate the semantic processing of Chinese radicals ...

Mechanism underlying cisplatin-induced ototoxicity

2013-08-07
Studies have shown that calpain participates in gentamicin-, neomycin- and kanamycin-induced inner ear cell apoptosis. Cisplatin has been shown to be an anticancer drug. However, cisplatin can lead to severe ototoxicity, induce cochlear cell apoptosis, and result in hearing decrease or loss, which limits the application of cisplatin in a clinical setting to a certain degree. A recent study by Liang Chang and colleagues from Jinzhou Central Hospital established a BALB/c mouse model of cisplatin-induced ototoxicity to detect the susceptibility to cisplatin-induced ototoxicity. ...

Caffeine 'traffic light': Do you want to know how much caffeine is in your drink?

2013-08-07
A team of researchers led by Prof. Young-Tae Chang from National University of Singapore and Prof. Yoon-Kyoung Cho from Ulsan National Institute of Science and Technology (UNIST), Korea, developed a fluorescent caffeine detector and a detection kit that lights up like a traffic light when caffeine is present in various drinks and solutions. The research work was published in Scientific Reports (Nature Publishing Group) on July 23, 2013. Caffeine drinks are ubiquitous and it would be unimaginable for many of us to go a day without caffeine. But certainly one begins to ...

Diamonds are a laser scientist's new best friend

2013-08-07
Once a James Bond fantasy, diamond-based lasers are now becoming a reality. Ground-breaking research is harnessing the unique properties of diamonds to develop a new generation of lasers that could lead to many benefits, from better treatment of skin complaints and diabetes-related eye conditions to improved pollution monitoring and aeronautical engineering. A University of Strathclyde team has developed a new type of high-performance, ultra-versatile Raman laser* that harnesses diamonds to produce light beams with more power and a wider range of colours than current ...

Trust thy neighbor

2013-08-07
Increases in population size may lead to a breakdown in social trust, according to Jordan Smith from North Carolina State University in the US. As local populations grow, local elected officials and national news media become less trusted, compared with friends and family, local churches and civic institutions. This 'trust deficit' has implications for long-term environmental and community planning. Smith's study is published online in Springer's journal Human Ecology. Smith studied three southern Appalachian mining communities during a period of change, amid growing ...

Novel beams made of twisted atoms

2013-08-07
Physicists have, for the first time, now built a theoretical construct of beams made of twisted atoms. These findings by Armen Hayrapetyan and colleagues at Ruprecht-Karls-University Heidelberg in Germany are about to be published in EPJ D. These so-called atomic Bessel beams can, in principle, have potential applications in quantum communication as well as in atomic and nuclear processes. The concept for twisted atom beams stems from a similar approach with twisted photon beams, which are currently used as optical tweezers, for instance. It was later extended to twisted ...

LAST 30 PRESS RELEASES:

Identification of chemical constituents and blood-absorbed components of Shenqi Fuzheng extract based on UPLC-triple-TOF/MS technology

'Glass fences' hinder Japanese female faculty in international research, study finds

Vector winds forecast by numerical weather prediction models still in need of optimization

New research identifies key cellular mechanism driving Alzheimer’s disease

Trends in buprenorphine dispensing among adolescents and young adults in the US

Emergency department physicians vary widely in their likelihood of hospitalizing a patient, even within the same facility

Firearm and motor vehicle pediatric deaths— intersections of age, sex, race, and ethnicity

Association of state cannabis legalization with cannabis use disorder and cannabis poisoning

Gestational hypertension, preeclampsia, and eclampsia and future neurological disorders

Adoption of “hospital-at-home” programs remains concentrated among larger, urban, not-for-profit and academic hospitals

Unlocking the mysteries of the human gut

High-quality nanodiamonds for bioimaging and quantum sensing applications

New clinical practice guideline on the process for diagnosing Alzheimer’s disease or a related form of cognitive impairment or dementia

Evolution of fast-growing fish-eating herring in the Baltic Sea

Cryptographic protocol enables secure data sharing in the floating wind energy sector

Can drinking coffee or tea help prevent head and neck cancer?

Development of a global innovative drug in eye drop form for treating dry age-related macular degeneration

Scientists unlock secrets behind flowering of the king of fruits

Texas A&M researchers illuminate the mysteries of icy ocean worlds

Prosthetic material could help reduce infections from intravenous catheters

Can the heart heal itself? New study says it can

Microscopic discovery in cancer cells could have a big impact

Rice researchers take ‘significant leap forward’ with quantum simulation of molecular electron transfer

Breakthrough new material brings affordable, sustainable future within grasp

How everyday activities inside your home can generate energy

Inequality weakens local governance and public satisfaction, study finds

Uncovering key molecular factors behind malaria’s deadliest strain

UC Davis researchers help decode the cause of aggressive breast cancer in women of color

Researchers discovered replication hubs for human norovirus

SNU researchers develop the world’s most sensitive flexible strain sensor

[Press-News.org] Scripps Research Institute scientists find key signal that guides brain development