Factors Affecting Macro-Structural Development in the Cerebral Cortex: The Potential Role of Tissue Removal Through Pruning and Apoptosis

Several theories have been developed to explain mechanisms of macro-structural development in the cerebral cortex, including external skull constraints, axonal tension, differential proliferation of neural progenitors, differential cortical expansion, and axonal pushing. These theories are not necessarily mutually exclusive, and some combination thereof may be required in order to fully explain and characterize complex folding, sulcal development and thinning in the cortex. This manuscript provides an overview of the leading theories of contributing factors to macro-structural cortical development, and presents additional potential contributing factors, including tissue removal through pruning and apoptosis. Although tissue removal has been proposed as a potentially major factor in microcephaly and megalencephaly-conditions with major deviations from healthy macro-structural cortical development-in this manuscript, it is proposed that tissue removal may be an important factor in healthy neurodevelopment, as well as in additional pathological conditions. This manuscript also presents the theory that tissue removal may be linked to learning. Potential consequences for a variety of pathological conditions, and potential relationships with previously established theories of macro-structural cortical development are discussed.