The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just ten per cent consisting of allocortex. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness.
Abnormal spindle-like microcephaly-associated protein, also known as abnormal spindle protein homolog or Asp homolog, is a protein that in humans is encoded by the ASPM gene. ASPM is located on chromosome 1, band q31 (1q31). The ASPM gene contains 28 exons and codes for a 3477 amino‐acid‐long protein. The ASPM protein is conserved across species including human, mouse, Drosophila, and C. elegans. Defective forms of the ASPM gene are associated with autosomal recessive primary microcephaly.
Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult. This process differs from prenatal neurogenesis.
Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and oligodendrocytes. Their cell bodies (somata) reside in the embryonic ventricular zone, which lies next to the developing ventricular system.
Neuropoiesis is the process by which neural stem cells differentiate to form mature neurons, astrocytes, and oligodendrocytes in the adult mammal. This process is also referred to as adult neurogenesis.
The Olduvai domain, known until 2018 as DUF1220 and the NBPF repeat, is a protein domain that shows a striking human lineage-specific (HLS) increase in copy number and appears to be involved in human brain evolution. The protein domain has also been linked to several neurogenetic disorders such as schizophrenia and increased severity of autism. In 2018, it was named by its discoverers after Olduvai Gorge in Tanzania, one of the most important archaeological sites for early humans, to reflect data indicating its role in human brain size and evolution.
Protein numb homolog is a protein that in humans is encoded by the NUMB gene. The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Four transcript variants encoding different isoforms have been found for this gene.
Transcription factor HES1 is a protein that is encoded by the Hes1 gene, and is the mammalian homolog of the hairy gene in Drosophila. HES1 is one of the seven members of the Hes gene family (HES1-7). Hes genes code nuclear proteins that suppress transcription.
RNA-binding protein Nova-1 is a protein that in humans is encoded by the NOVA1 gene.
Numb-like protein is a protein that in humans is encoded by the NUMBL gene.
Homeobox protein EMX1 is a protein that in humans is encoded by the EMX1 gene. The transcribed EMX1 gene is a member of the EMX family of transcription factors. The EMX1 gene, along with its family members, are expressed in the developing cerebrum. Emx1 plays a role in specification of positional identity, the proliferation of neural stem cells, differentiation of layer-specific neuronal phenotypes and commitment to a neuronal or glial cell fate.
Gyrification is the process of forming the characteristic folds of the cerebral cortex. The peak of such a fold is called a gyrus, and its trough is called a sulcus. The neurons of the cerebral cortex reside in a thin layer of gray matter, only 2–4 mm thick, at the surface of the brain. Much of the interior volume is occupied by white matter, which consists of long axonal projections to and from the cortical neurons residing near the surface. Gyrification allows a larger cortical surface area and hence greater cognitive functionality to fit inside a smaller cranium. In most mammals, gyrification begins during fetal development. Primates, cetaceans, and ungulates have extensive cortical gyri, with a few species exceptions, while rodents generally have none. Gyrification in some animals, for example the ferret, continues well into postnatal life.
Eomesodermin also known as T-box brain protein 2 (Tbr2) is a protein that in humans is encoded by the EOMES gene.
A cerebral organoid, or brain organoid, describes an artificially grown, in vitro, miniature organ resembling the brain. Cerebral organoids are created by culturing pluripotent stem cells in a three-dimensional rotational bioreactor, and they develop over a course of months. The brain is an extremely complex system of heterogeneous tissues and consists of a diverse array of neurons. This complexity has made studying the brain and understanding how it works a difficult task in neuroscience, especially when it comes to neurodegenerative diseases. The purpose of creating an in vitro neurological model is to study these diseases in a more simple and variable space. This 3D model is free of many potential in vivo limitations. The varying physiology between human and other mammalian models limits the scope of study in neurological disorders. Cerebral organoids are synthesized tissues that contain several types of nerve cells and have anatomical features that recapitulate regions of the cortex observed in brains. Cerebral organoids are most similar to layers of neurons called the cortex and choroid plexus. In some cases, structures similar to the retina, meninges and hippocampus can form. Stem cells have the potential to grow into many different types of tissues, and their fate is dependent on many factors. Below is an image showing some of the chemical factors that can lead stem cells to differentiate into various neural tissues; a more in-depth table of generating specific organoid identity has been published since. Similar techniques are used on stem cells used to grow cerebral organoids.
Epigenetics is the study of heritable changes in gene expression which do not result from modifications to the sequence of DNA. Neurogenesis is the mechanism for neuron proliferation and differentiation. It entails many different complex processes which are all time and order dependent. Processes such as neuron proliferation, fate specification, differentiation, maturation, and functional integration of newborn cells into existing neuronal networks are all interconnected. In the past decade many epigenetic regulatory mechanisms have been shown to play a large role in the timing and determination of neural stem cell lineages.
Proneural genes encode transcription factors of the basic helix-loop-helix (bHLH) class which are responsible for the development of neuroectodermal progenitor cells. Proneural genes have multiple functions in neural development. They integrate positional information and contribute to the specification of progenitor-cell identity. From the same ectodermal cell types, neural or epidermal cells can develop based on interactions between proneural and neurogenic genes. Neurogenic genes are so called because loss of function mutants show an increase number of developed neural precursors. On the other hand, proneural genes mutants fail to develop neural precursor cells.
In vertebrates, the ventricular zone (VZ) is a transient embryonic layer of tissue containing neural stem cells, principally radial glial cells, of the central nervous system (CNS). The VZ is so named because it lines the ventricular system, which contains cerebrospinal fluid (CSF). The embryonic ventricular system contains growth factors and other nutrients needed for the proper function of neural stem cells. Neurogenesis, or the generation of neurons, occurs in the VZ during embryonic and fetal development as a function of the Notch pathway, and the newborn neurons must migrate substantial distances to their final destination in the developing brain or spinal cord where they will establish neural circuits. A secondary proliferative zone, the subventricular zone (SVZ), lies adjacent to the VZ. In the embryonic cerebral cortex, the SVZ contains intermediate neuronal progenitors that continue to divide into post-mitotic neurons. Through the process of neurogenesis, the parent neural stem cell pool is depleted and the VZ disappears. The balance between the rates of stem cell proliferation and neurogenesis changes during development, and species from mouse to human show large differences in the number of cell cycles, cell cycle length, and other parameters, which is thought to give rise to the large diversity in brain size and structure.
Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs), radial glial cells (RGCs), basal progenitors (BPs), intermediate neuronal precursors (INPs), subventricular zone astrocytes, and subgranular zone radial astrocytes, among others.
Jürgen Knoblich is a German molecular biologist. Since 2018, he is Scientific Director of the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences in Vienna.
Paola Arlotta is an Italian molecular biologist and neuroscientist who is Golub Family Professor and Chair of the Stem Cell and Regenerative Biology Department at Harvard University. Arlotta leads the neuroscience program within the Harvard Stem Cell Institute and is a member of Stanley Center for Psychiatric Research within the Broad Institute. Arlotta's research focuses on understanding the genetic and molecular mechanisms underlying development of the brain's cerebral cortex, such that she can apply this knowledge to regenerate the brain in disease states.
