http://www.neuroscience.ubc.ca/CourseMat/Kriegstein-Develop_H_Cortx.pdf

Development and Evolution of the Human Neocortex

The cerebral cortex of large mammals undergoes massive surface area expansion and folding during development. Specific mechanisms to orchestrate the growth of the cortex in surface area rather than in thickness are likely to exist, but they have not been identified. Analyzing multiple species, we have identified a specialized type of progenitor cell that is exclusive to mammals with a folded cerebral cortex, which we named intermediate radial glia cell (IRGC). IRGCs express Pax6 but not Tbr2, have a radial fiber contacting the pial surface but not the ventricular surface, and are found in both the inner subventricular zone and outer subventricular zone (OSVZ). We find that IRGCs are massively generated in the OSVZ, thus augmenting the numbers of radial fibers. Fanning out of this expanding radial fiber scaffold promotes the tangential dispersion of radially migrating neurons, allowing for the growth in surface area of the cortical sheet. Accordingly, the tangential expansion of particular cortical regions was preceded by high proliferation in the underlying OSVZ, whereas the experimental reduction of IRGCs impaired the tangential dispersion of neurons and resulted in a smaller cortical surface. Thus, the generation of IRGCs plays a key role in the tangential expansion of the mammalian cerebral cortex.

/pdf/a-role-for-intermediate-radial-glia-in-the-tangential-1me1ak0rgu.pdf

A Role for Intermediate Radial Glia in the Tangential Expansion of the Mammalian Cerebral Cortex

The size and extent of folding of the mammalian cerebral cortex are important factors that influence a species' cognitive abilities and sensorimotor skills. Studies in various animal models and in humans have provided insight into the mechanisms that regulate cortical growth and folding. Both protein-coding genes and microRNAs control cortical size, and recent progress in characterizing basal progenitor cells and the genes that regulate their proliferation has contributed to our understanding of cortical folding. Neurological disorders linked to disruptions in cortical growth and folding have been associated with novel neurogenetic mechanisms and aberrant signalling pathways, and these findings have changed concepts of brain evolution and may lead to new medical treatments for certain disorders.

/pdf/growth-and-folding-of-the-mammalian-cerebral-cortex-from-5ayiqphrdd.pdf

Growth and folding of the mammalian cerebral cortex: from molecules to malformations

The most striking, interesting, yet poorly understood gross morphological features of the cerebral hemispheres in mammals are the diverse and complex arrangements of their cortical gyri and sulci (Fig. 1). Among mammals, the spinal cord and brain-stem nuclei are morphologically quite similar, despite variations in size. However, during evolution, the cerebrum and cerebellum have undergone marked variations in size, shape, and convolutional complexity (Fig. 2). External morphological features of mammalian brains have long been utilized to judge not only the degree of phylogenetic development, but also the nature and level of complexity of brain functions. The great variety of living mammals exhibit a corresponding variety of brain shapes, sizes, and patterns of fissuration and convolution of the cerebral neocortex. The view has consistently been expressed that animals with brains having greater amounts of convoluted cerebral neocortex were more intelligent as well as perceptually and behaviorally more complex.

Why Does Cerebral Cortex Fissure and Fold

The convolutions of the mammalian cortex are one of its most intriguing characteristics. Their pattern is very distinctive for different species, and there seems to be a remarkable relationship between convolutions and the architectonic and functional regionalization of the cerebral cortex. Yet the mechanisms behind the development of convolutions and their association with the cortical regionalization are poorly understood. Here we propose a morphogenetic model for the development of cortical convolutions based on the structure of the cortex as a closed surface with glial and axonal fibres pulling radially, the fundamental mechanical properties of cortex and fibres (elasticity and plasticity), and the growth of the cortical surface. The computer simulations of this model suggest that convolutions are a natural consequence of cortical growth. The model reproduces several aspects of convolutional development, such as the relationship between cortical surface and brain volume among mammals, the period of compensation in the degree of convolution observed in gyrencephalic brains and the dependence of the degree of convolution on cortical thickness. We have also studied the effect of early cortical regionalization on the development of convolutions by introducing geometric, mechanic and growth asymmetries in the model. The morphogenetic model is thus able to reproduce the gradients in the degree of convolution, the development of primary, secondary and tertiary convolution, and the overproduction of sulci observed in animals with altered afferent cortical connections.

/pdf/a-morphogenetic-model-for-the-development-of-cortical-1lxdug9vze.pdf

A Morphogenetic Model for the Development of Cortical Convolutions

The internal changes within a developing gyrus of the ferret cerebral cortex were studied by recording (i) the changing length and direction of the radial tissue lines and (ii) the emergence of the tangential banding of the classical six cortical layers. Together these lines provided a coordinate net whose deformations during development gave an indication of the differential growth occurring within a gyrus. The changes in these features suggested that a gyrus was initiated by an area of local growth appearing in the subplate and then in the suprajacent segment of cortical plate. During subsequent growth there was tangential spreading of the more mature tissue at the gyral crown while at the site of the future sulci the cortical plate remained immature and growth was retarded. During later stages the majority of tangential growth occurred in the parasulcal area. At this site a very much thinner cortex was generated from a segment of cortical plate of the same depth and degree of nuclear crowding as elsewhere, implying that growth here was resolved into tangential spreading. The cells and fibres of the deeper cortical layers of the sulcal cortex eventually became tangentially orientated suggesting that they subserved a commissural function between the columnar systems of adjacent gyri. At the scale prevailing in the ferret, gyrus formation was seen as a configuration which tended to conserve both the total length of the cortical columns and the depth of the individual cortical layers.

G. M. Mcsherry

Papers

Gyrus formation in the cerebral cortex of the ferret. II: Description of the internal histological changes