Key Points
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The neocortex is the most recently evolved part of the cerebral cortex. Its development has been well studied for some time, partly because of its striking organization into six distinct neuronal layers and partly because its development is disrupted in several human diseases.
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Only recently have significant advances been made in our understanding of the molecular mechanisms that determine neocortical development, mainly based on genetic studies of human diseases that affect cortical development, such as lissencephaly, and of mouse mutants with cortical-layering defects. These studies have provided molecular biologists with several key proteins that are required for proper neuronal migration in the cortex.
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Genetic and cell-biological studies have identified how several key proteins that are required for the proper radial migration of neurons in the cortex, such as reelin, lissencephaly 1 and cyclin-dependent kinase 5, modulate signalling pathways that are involved in neuronal migration and adhesion. Recent work is beginning to identify how these pathways interact and modulate one another.
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Further advances in our understanding of neuronal migration and how the pathways that regulate cortical layering are integrated will be best addressed by a combination of both genetic and developmental approaches.
Abstract
Although the basic principles of neocortical development have been known for quite some time, it is only recently that our understanding of the molecular mechanisms that are involved has improved. Such understanding has been facilitated by genetic approaches that have identified key proteins involved in neocortical development, which have been placed into signalling pathways by molecular and cell-biological studies. The challenge of current research is to understand the manner in which these various signalling pathways are interconnected to gain a more comprehensive picture of the molecular intricacies that govern neocortical development.
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cytoplasmic dynein heavy chain
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OMIM
isolated lissencephaly sequence
lissencephaly with cerebellar hypoplasia
FURTHER INFORMATION
Encyclopedia of Life Sciences
Glossary
- NEOCORTEX
-
The most recently evolved part of the cerebral cortex. It is believed to orchestrate high-level motor, sensory and cognitive functions.
- RADIAL DIRECTION
-
The movement of neurons from the inner to the outer brain surface. The inner brain surface lines the brain ventricles, and the outer brain surface lines the pia.
- TANGENTIAL DIRECTION
-
The movement of neurons parallel to the inner or outer brain surface.
- PIAL SURFACE
-
The outer brain surface (the pia is a membrane that covers the brain underneath the skull).
- LOCOMOTION
-
A cell movement along glial fibre tracts in which the length of the leading process of a cell is maintained, as the cell soma and the leading edge move in concert.
- RADIAL GLIA CELL
-
Precursor cell of the developing central nervous system (CNS). They give rise to glia cells (specialized connective tissue cells of the CNS) and also differentiate into neurons.
- NUCLEAR TRANSLOCATION
-
A neuronal movement that is independent of glial fibre tracts, in which the cell nucleus moves towards the leading edge, such that the leading process of the cell (the distance between the apex of the cell soma and the leading edge) shortens over time.
- AGYRIA
-
The absence of gyri (folds in the surface of the brain).
- PACHYGYRIA
-
A reduced number of broadened gyri.
- HETEROTOPIA
-
A group of abnormally placed cells. In the context of neuronal-migration defects, it refers to cells that are out of place in the cortex in either the grey or the white matter.
- SUBCORTICAL BAND HETEROTOPIA
-
(SBH). A group of heterotopic neurons that form in the white matter.
- WD40 REPEAT
-
A conserved finger-like structural motif that consists of repeats of tryptophan (W) and aspartic acid (D). In LIS1, there are seven WD40 repeats that are postulated to assume a 'propeller wheel' configuration similar to other WD40 repeat proteins.
- DYNEIN
-
A minus-end-directed microtubule motor protein that can move along microtubules and carry cell cargo along them towards the cell centre, where the minus ends of the microtubules are positioned. When it is tethered in the periphery to the plasma membrane or to the non-microtubule cytoskeleton, it can transport cell cargo towards the cell periphery.
- NUCLEOKINESIS
-
A process in which nuclei migrate towards the tips of the developing hyphae of Aspergillus nidulans under conditions of nutrient deprivation. This migration of the nuclei is an example of nuclear translocation and is disrupted in nuclear distribution (nud) mutants.
- LEADING EDGE
-
The thin margin of a lamellipodium that spans the area of the cell from the plasma membrane to about 1 μm back into the lamellipodium. Lamellipodia are flattened, sheet-like projections from the surface of a cell, which are often associated with cell migration.
- CENTROSOME
-
The main microtubule-organizing centre of animal cells.
- RGD MOTIF
-
A peptide motif that consists of the amino acids arginine (R), glycine (G) and aspartate (D), which is found in many ligands that bind to integrins.
- N-CADHERINS
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Adhesion molecules that bind to each other in a calcium-dependent manner, and thereby connect nerve cells to each other. N-cadherin is stabilized on the cell surface by β-catenin, which links N-cadherin to the actin cytoskeleton.
- ADHERENS JUNCTIONS
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Points of cell–cell contact. In adherens junctions, a member of the cadherin family usually binds to β-catenin, which in turn is linked to the cortical actin cytoskeleton through α-catenin.
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Gupta, A., Tsai, LH. & Wynshaw-Boris, A. Life is a journey: a genetic look at neocortical development. Nat Rev Genet 3, 342–355 (2002). https://doi.org/10.1038/nrg799
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DOI: https://doi.org/10.1038/nrg799
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