Scripps Research Institute Scientists Find Key Signal that Guides Brain Development 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.
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).
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the worlds large
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
07/10/2026
Dalet, a leading technology and service provider for media-rich organizations, today announced the latest Long-Term Supported (LTS) release of Dalet Flex. Build...
06/09/2026
June 9 2026, 23:00 (PDT) Dolby and MagentaTV Bring Fans Closer to the FIFA Worl...
19/08/2026
As the cost of IP nears price parity with traditional SDI, Reynolds argues that ...
19/08/2026
A private 5G bubble was chosen instead of traditional broadcast RF for the race ...
19/08/2026
(L-R) Rafael Manuel and Isabel Sicat attend the Filipi ana premiere during the 2026 Sundance Film Festival at The Ray Theatre on January 23, 2026, in Park Cit...
19/08/2026
Studio owners invited to have their say on rates cuts
The Music Producers Guild (MPG) are inviting UK-based studios to take part in an in-depth survey that ...
19/08/2026
Vintage-inspired desktop interface revealed
Harrison's latest hardware offering sees them head into the world of audio interfaces, delivering a 10-in/12...
19/08/2026
Granular effect remains locked to scale and tempo
Described as your dream granular effect , Minimal Audio's latest creation is capable of turning any s...
19/08/2026
First polyphonic SWAM instrument incoming
Audio Modeling's latest physical-modelling orchestral instrument is just around the corner, and is now availab...
19/08/2026
World Cup Games Generate 84 Billion Minutes Across FOX, Fox Sports 1 and NBCU...
19/08/2026
July brought typical peak-holiday drops in viewership, driven primarily by viewers stepping away from screens and a visible decline in reach across both traditi...
19/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/08/2026
Henry joins BCE as the company accelerates its commercial strategy and expands its international presence across the media, broadcast and technology markets. He...
19/08/2026
iWedia, a leading provider of software solutions for connected TV devices, today announced a major milestone in Android platform optimization with the successfu...
19/08/2026
NTP Technology announces that ST 2110-30 audio-over-IP connectivity with AES67 and RAVENNA capabilities is now available for the brand's world-class audio i...
19/08/2026
Net Insight has been selected to provide its Nimbra platform by the service provider Big Blue Marble, formerly ORS Group, as the core media transport solution f...
19/08/2026
LiveU has supported Coventry City FC and several other top-flight UK football clubs through one of their most demanding live production challenges of the year, ...
19/08/2026
Nature Seekers Documentary Shot with Blackmagic URSA Cine 12K LF
Brie Clayton August 18, 2026
0 Comments
Filming endangered turtles required camera...
19/08/2026
Neyrinck Brings D-Control Consoles Back to Life on Apple Silicon with D-Control ...
19/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/08/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/08/2026
Riedel Communications today announced that Edith Cowan University (ECU) in Perth, Australia, implemented a comprehensive communications infrastructure that brin...
19/08/2026
QuickLink, a leading provider of award-winning video production and remote guest contribution solutions, will spotlight a major leap forward in remote guest con...
19/08/2026
Integrated platform melds media asset management, playout automation and newsroom workflows
EMAM, PlayBox Neo and SNEWS have officially launched Nuvex, a conne...
19/08/2026
Screen Australia releases the Private Investment Toolkit to strengthen screen in...
19/08/2026
Do Aussies truly value local content? Unpacking Screen Currency 2026 with Deirdr...
19/08/2026
There's an early Christmas gift for Bookish fans, as UKTV confirms the re-commission of the hit U&alibi drama, created by and starring Mark Gatiss. Viewers ...
19/08/2026
Wednesday 19 August 2026
Sky gives sports fans the chance to watch multiple liv...
19/08/2026
On Saturday September 5 Katie Taylor will step into the ring for the fight of her life against Flora Pili in front of 80,000 fans in Croke Park. A legendary fig...
18/08/2026
SportStream 2026, a free three-day virtual event, will take place September 15-17. One registration provides access to all three days of live programming and on...
18/08/2026
BeckTV will introduce BeckFlow to the European market at IBC2026, demonstrated on the Providius stand (10.F53).
BeckFlow is a web-based schematic documentation...
18/08/2026
Boland Communications will introduce a SMPTE ST 2110 input option for its 4K monitors at IBC2026, along with a new 55-inch super-narrow bezel display for video ...
18/08/2026
Dolby Laboratories and the Seattle Seahawks have announced a partnership integrating Dolby OptiView into the Seahawks' live streaming coverage, making the S...
18/08/2026
For BMG Executive Producer of Sports Production, Graham Taylor, producing live s...
18/08/2026
TMRW Sports has appointed Rufus Hack as President of Golf, a newly created role in which he will lead the company's golf businesses including TGL presented ...
18/08/2026
SMT will provide race technology for FOX Sports' coverage of the Freedom 250 Grand Prix of Washington, D.C. on August 23, when the NTT INDYCAR SERIES races ...
18/08/2026
The live, YouTube-native roundtables combine fan voices, credentialed reporters,...
18/08/2026
Behind The Mic provides a roundup of recent news regarding on-air talent, includ...
18/08/2026
The industry legend sounds off on replacing the Heat's iconic Medusa score...
18/08/2026
William F. Rasmussen, the sports fan-turned broadcaster and entrepreneur whose out-of-the-box idea of a 24-hour cable sports network, ESPN, changed forever the ...
18/08/2026
DAZN Group has completed its acquisition of ViewLift, a provider of streaming and digital solutions for sports content owners. The acquisition was first announc...
18/08/2026
The American Association of Professional Baseball (AAPB) has added SI TV, Sports Illustrated's 24/7 streaming channel, as a broadcast partner for the remain...
18/08/2026
The Esports Foundation has announced that the inaugural Esports Nations Cup (ENC), originally scheduled for November 2026 in Riyadh, will be postponed to Novemb...
18/08/2026
Diversified has announced a new Global Managed Services Practice, consolidating the company's managed services capabilities into one organization. Rob Mello...
18/08/2026
Appear has completed a proof of concept with Thoroughbred Racing Productions (TRP), demonstrating multi-camera remote live production over bonded 5G cellular an...
Scripps Research Institute Scientists Find Key Signal that Guides Brain Development 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.
