The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans. (Agencies)
"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 The Scripps Research Institute (TSRI)'s Department of Molecular and Cellular Neuroscience and director of the Dorris Neuroscience Center at TSRI.
The discovery appearing in the journal Neuron is likely to aid research on autism, schizophrenia and other psychiatric conditions.
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.
Previously, scientists had discovered a key signaling protein, reelin, which CR cells secrete and baby neocortical neurons must detect to migrate properly. There have been hints since then that CR cells and baby neocortical neurons exchange other molecular signals, too.
In a study published in 2011, Mueller and his laboratory colleagues discovered that reelin 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. One set of candidates were the nectins - cell-adhesion proteins known to work with cadherins in other contexts.
"We observed that nectin1 is expressed specifically by CR cells and nectin3 by migrating neurons. At the same time, we knew from previous research that nectin1 and nectin3 are preferred binding partners," said lead author Cristina Gil-Sanz.
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.
The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans.