Cerebral cortex expansion and folding: what have we learned?

Abstract

One of the most prominent features of the human brain is the fabulous size of the cerebral cortex and its intricate folding. Cortical folding takes place during embryonic development and is important to optimize the functional organization and wiring of the brain, as well as to allow fitting a large cortex in a limited cranial volume. Pathological alterations in size or folding of the human cortex lead to severe intellectual disability and intractable epilepsy. Hence, cortical expansion and folding are viewed as key processes in mammalian brain development and evolution, ultimately leading to increased intellectual performance and, eventually, to the emergence of human cognition. Here, we provide an overview and discuss some of the most significant advances in our understanding of cortical expansion and folding over the last decades. These include discoveries in multiple and diverse disciplines, from cellular and molecular mechanisms regulating cortical development and neurogenesis, genetic mechanisms defining the patterns of cortical folds, the biomechanics of cortical growth and buckling, lessons from human disease, and how genetic evolution steered cortical size and folding during mammalian evolution.

Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulating Aldh1a3 pre-mRNA 3'-end processing

“…Importantly, the impaired balance between self-renewal and differentiation in Khdrbs1 -/- mice results in depletion of the NPC pool and reduced expansion of the neocortex. Since altered neurogenesis and cortical development are associated to severe neuronal disorders like epilepsy, schizophrenia and autism (Sun and Hevner, 2014; Fernández et al, 2016), our findings suggest that fine-tuned regulation of Sam68 expression represents a safeguard mechanism during brain development.…”

“…These divisions of neural precursors need to be tightly modulated, as proper regulation of neurogenesis is of paramount importance to achieve the right number of neurons and the correct expansion and stratification of the cortex during development. In particular, fine-tuned control of NPC fate is required to balance self-renewing divisions with asymmetric divisions (Taverna et al, 2014; Fernández et al, 2016). Conversely, dysregulation of neurogenesis can result in developmental disorders linked to neurological pathologies (Sun and Hevner, 2014).…”

Dishing out mini-brains: Current progress and future prospects in brain organoid research

“…Even this very simplified description of human neocortical neurogenesis (for details of cell-biological features of neural progenitors, please see recent reviews (de Juan Romero and Borrell, 2015, Fernández et al, 2016, Florio and Huttner, 2014, Lui et al, 2011, Paridaen and Huttner, 2014, Taverna et al, 2014)) hopefully gives some indication of the complexity of cell biological and morphological changes that need to take place in order for a mature and functional adult brain to develop. Therefore it is remarkable that some in vitro protocols have managed to faithfully recapitulate a significant portion of the neurogenic period.…”

Surface creasing of soft elastic continua as a Kosterlitz-Thouless transition

“…Finite-length creases can be described in the same framework. Our predictions for crease surface profiles and onset strain agree with previous experiments and simulations, and further experimental tests are proposed.PACS numbers: 46.35.+z, 62.20.mq, 68.35.Rh, 82.60.Nh, 87.15.Zg Cusped inward folds known as creases form on compressed surfaces of a variety of soft elastic materials [1], including natural rubber [2,3], polymer gels [4-6], silicone elastomers [7][8][9][10][11][12], starchy foods [13,14], and the developing mammalian brain [11,12,15,16]. In the latter context, creases are called "sulci".…”