Scientists find a critical signal that guides brain development.

The blog post from ScienceDaily discusses a study conducted by scientists at The Scripps Research Institute (TSRI) who have decoded a crucial molecular signal that guides the development of the neocortex, a critical brain region. The neocortex is the brain’s largest and most recently evolved region, responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness, and more.

The researchers found that this signal helps guide the migration of baby neurons through the developing neocortex. These neurons are born from stem-like cells at the bottom of the neocortex and then migrate upward, being directed to their proper places in the neocortex’s six-layered, columnar structure by special guide cells called Cajal-Retzius (CR) cells.

The team discovered that the hookup of nectin1 on CR cells with nectin3 on baby neurons is essential for proper neuronal migration. This direct nectin-to-nectin connection is effectively part of the reelin signaling pathway linked to autism, depression, schizophrenia, and Alzheimer’s in humans.

This study represents a significant step towards understanding neuronal migration in the neocortex and is likely relevant to studying developmental brain diseases.

The blog post from ScienceDaily discusses a study conducted by scientists at The Scripps Research Institute (TSRI) who have decoded a crucial molecular signal that guides the development of the neocortex, a key brain region. The neocortex is the brain’s largest and most recently evolved region, responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness, and more.

The researchers found that this signal helps guide the migration of baby neurons through the developing neocortex. These neurons are born from stem-like cells at the bottom of the neocortex and then migrate upward, being directed to their proper places in the neocortex’s six-layered, columnar structure by special guide cells called Cajal-Retzius (CR) cells.

The team discovered that the hookup of nectin1 on CR cells with nectin3 on baby neurons is essential for proper neuronal migration. This direct nectin-to-nectin connection is effectively part of the reelin signaling pathway linked to autism, depression, schizophrenia, and Alzheimer’s in humans.

The study also found that reelin, an essential signaling protein, 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 was the lectins — cell-adhesion proteins known to work with cadherins in other contexts. The researchers observed that nectin1 is explicitly expressed by CR cells and nectin3 by migrating neurons. The experiments confirmed that the hookup of nectin1 on CR cells with nectin3 on baby neurons is essential for proper neuronal migration. 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 works essentially via nectin3.

The finding points to the possibility of other cell-specific pairings that work via generic Cdh2-to-Cdh2 adhesions in brain development. The new study represents a significant step toward the complete 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 have also been linked to disorders including schizophrenia and autism.

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