Gyrification is the process of forming the characteristic folds of the cerebral cortex. The peak of such a fold is called a gyrus (plural: gyri), and its trough is called a sulcus (plural: sulci). In most mammals, gyrification usually begins during embryogenesis and fetal development when neurogenesis is building the neuronal cortical layers, although some mammals, such as the ferret, are precociously born and develop gyri mainly after birth. Most rodents do not form cortical gyri. Primates, carnivores, cetaceans, and ungulates have extensive cortical gyri, with a few species exceptions, and gyrification in these animals continues well into postnatal life. Gyrification permits a larger cortical surface area and hence greater cognitive function in a smaller cranium.
A cerebral cortex lacking surface convolutions is said to be lissencephalic, meaning 'smooth-brained'. During embryonic development, all mammalian brains begin as lissencephalic structures derived from the neural tube. As development proceeds, gyri and sulci begin to take shape with the emergence of deepening indentations on the surface of the cortex. Not all gyri begin to develop at the same time, but instead the primary cortical gyri form first (beginning as early as gestational week 10 in human), followed by secondary and tertiary gyri later in development. One of the first and most prominent sulci is the lateral sulcus (also known as the lateral fissure or Sylvian fissure).
The mechanisms of cortical gyrification are not well understood, and several hypotheses are debated in the scientific literature. A popular hypothesis dating back to the time of His and Retzius in the late 19th century asserts that mechanical buckling forces due to the expanding brain tissue cause the cortical surface to fold. An alternative involving axonal tension forces has also gained support. More recently, a modification of the mechanical buckling hypothesis posits that certain progenitor cells generate abundant neurons destined for the outer cortical layers, causing greater surface area increase in the outer layers compared with the inner cortical layers. However it remains unclear how this may work without further mechanistic elements. The pattern of cortical gyri and sulci is not random; most of the major convolutions are conserved between individuals and many are also found across species. This reproducibility may suggest that genetic mechanisms can specify the developmental location of the major gyri; indeed, studies of monozygotic and dizygotic twins support the idea. Studies have attempted to induce cortical gyrification in the mouse, which normally does not develop cortical convolutions, with varying degrees of success. The first viable mouse model of gyrencephaly was reported in 2013, when fully layered, organized neocortical gyri were induced to form in the mouse brain. Furthermore, induction of gyrus formation occurred before axons could play a role, arguing against the axonal tension hypothesis during primary gyrification. Nevertheless, in primates many tertiary gyri do not form until well after the last cortical neurons have been generated, and it is likely that a number of factors, including axonal innervation, contribute to the maturation of cortical gyri. These studies together showed that changes in stem cell dynamics can have profound effects on brain structure, and provide potential clues to the evolution of gyrencephaly.
Cortical stem cells, known as radial glial cells (RGC)s, reside in the ventricular zone and generate the excitatory glutamatergic neurons of the cerebral cortex. These cells rapidly proliferate through self-renewal at early developmental stages, expanding the progenitor pool and increasing cortical surface area. Cortical neurogenesis begins to deplete this pool of progenitor cells, subject to the influences of genetic and environmental cues such as fibroblast growth factors (FGF)s and Notch proteins. RGCs generate intermediate neuronal precursors that divide further in the subventricular zone (SVZ), amplifying the number of cortical neurons being produced. A second class of RGC, termed basal RGCs (bRGC)s, forms a third progenitor pool in the outer SVZ. Basal RGCs are generally much more abundant in higher mammals. The current scientific literature points to differences in the dynamics of proliferation and neuronal differentiation in each of these progenitor zones across mammalian species, and such differences may account for the large differences in cortical size and gyrification among mammals.
Various brains. Clockwise from top left: Adult rhesus; Adult mouse; Midgestation human; Newborn human; Adult human.
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