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Ventricular Zone
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 ...
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Stem Cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type. In mammals, roughly 50–150 cells make up the inner cell mass during the blastocyst stage of embryonic development, around days 5–14. These have stem-cell capability. ''In vivo'', they eventually differentiate into all of the body's cell types (making them pluripotent). This process starts with the differentiation into the three germ layers – the ectoderm, mesoderm and endoderm – at the gastrulation stage. How ...
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Microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it may develop in the first few years of life. Since brain growth is correlated with head growth, people with this disorder often have an intellectual disability, poor motor function, poor speech, abnormal facial features, seizures and dwarfism. The disorder is caused by a disruption to the genetic processes that form the brain early in pregnancy, though the cause is not identified in most cases. Many genetic syndromes can result in microcephaly, including chromosomal and single-gene conditions, though almost always in combination with other symptoms. Mutations that result solely in microcephaly (primary microcephaly) exist but are less common. External toxins to the embryo, such as alcohol during pregnancy or vertically transmitted inf ...
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Protomap (neuroscience)
The Protomap is a primordial molecular map of the functional areas of the mammalian cerebral cortex during early embryonic development, at a stage when neural stem cells are still the dominant cell type. The protomap is a feature of the ventricular zone, which contains the principal cortical progenitor cells, known as radial glial cells. Through a process called ' cortical patterning', the protomap is patterned by a system of signaling centers in the embryo, which provide positional information and cell fate instructions. These early genetic instructions set in motion a development and maturation process that gives rise to the mature functional areas of the cortex, for example the visual, somatosensory, and motor areas. The term protomap was coined by Pasko Rakic. The ''protomap hypothesis'' was opposed by the ''protocortex hypothesis'', which proposes that cortical proto-areas initially have the same potential, and that regionalization in large part is controlled by external i ...
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Cortical Patterning
Cortical patterning is a field of developmental neuroscience which aims to determine how the various functional areas of the cerebral cortex are generated, what size and shape they will be, and how their spatial pattern across the surface of the cortex is specified. Early brain lesion studies indicated that different parts of the cortex served different cognitive functions, such as visual, somatosensory, and motor functions, beautifully assimilated by Brodmann in 1909. Today the field supports the idea of a ' protomap', which is a molecular pre-pattern of the cortical areas during early embryonic stages. The protomap is a feature of the cortical ventricular zone, which contains the primary stem cells of the cortex known as radial glial cells. A system of signaling centers, positioned strategically at the midline and edges of the cortex, produce secreted signaling proteins that establish concentration gradients in the cortical primordium. This provides positional information f ...
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Base Excision Repair
Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky helix-distorting lesions. BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch (where a single nucleotide is replaced) or long-patch BER (where 2–10 new nucleotides are synthesized). Lesions processed by BER Single bases in DNA can be chemically damaged by a variety of mechanisms, the most common ones being deamination, oxidation, ...
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TET Enzymes
The TET enzymes are a family of ten-eleven translocation (TET) methylcytosine dioxygenases. They are instrumental in DNA demethylation. 5-Methylcytosine (see first Figure) is a methylated form of the DNA base cytosine (C) that often regulates gene transcription and has several other functions in the genome. Demethylation by TET enzymes (see second Figure), can alter the regulation of transcription. The TET enzymes catalyze the hydroxylation of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and can further catalyse oxidation of 5hmC to 5-formylcytosine (5fC) and then to 5-carboxycytosine (5caC). 5fC and 5caC can be removed from the DNA base sequence by base excision repair and replaced by cytosine in the base sequence. TET enzymes have central roles in DNA demethylation required during embryogenesis, gametogenesis, memory, learning, addiction and pain perception. TET proteins The three related ''TET'' genes, '' TET1'', ''TET2'' and ''TET3'' code res ...
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DNA Demethylation
For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence or, in replicating cells, by preventing addition of methyl groups to DNA so that the replicated DNA will largely have cytosine in the DNA sequence (5mC will be diluted out). Methylated cytosine is frequently present in the linear DNA sequence where a cytosine is followed by a guanine in a 5' → 3' direction (a CpG site). In mammals, DNA methyltransferases (which add methyl groups to DNA bases) exhibit a strong sequence preference for cytosines at CpG sites. There appear to be more than 20 million CpG dinucleotides in the human genome (see genomic distribution). In mammals, on average, 70% to 80% of CpG cytosines are methylated, though the level of methylation varies with different tissues. Methylated cytosines often occur in group ...
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DNA Methyltransferase
In biochemistry, the DNA methyltransferase (DNA MTase, DNMT) family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl methionine (SAM) as the methyl donor. Classification Substrate MTases can be divided into three different groups on the basis of the chemical reactions they catalyze: * m6A - those that generate N6-methyladenine * m4C - those that generate N4-methylcytosine * m5C - those that generate C5-methylcytosine m6A and m4C methyltransferases are found primarily in prokaryotes (although recent evidence has suggested that m6A is abundant in eukaryotes). m5C methyltransfereases are found in some lower eukaryotes, in most higher plants, and in animals beginning with the echinoderms. The m6A methyltransferases (N-6 adenine-specific DNA methylase) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines ...
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Cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an amine group at position 4 and a keto group at position 2). The nucleoside of cytosine is cytidine. In Watson-Crick base pairing, it forms three hydrogen bonds with guanine. History Cytosine was discovered and named by Albrecht Kossel and Albert Neumann in 1894 when it was hydrolyzed from calf thymus tissues. A structure was proposed in 1903, and was synthesized (and thus confirmed) in the laboratory in the same year. In 1998, cytosine was used in an early demonstration of quantum information processing when Oxford University researchers implemented the Deutsch-Jozsa algorithm on a two qubit nuclear magnetic resonance quantum computer (NMRQC). In March 2015, NASA scientists reported the formation of cytosine, along with uracil and ...
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Neural Stem Cell
Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor stem cells persist in highly restricted regions in the adult vertebrate brain and continue to produce neurons throughout life. Differences in the size of the central nervous system are among the most important distinctions between the species and thus mutations in the genes that regulate the size of the neural stem cell compartment are among the most important drivers of vertebrate evolution. Stem cells are characterized by their capacity to differentiate into multiple cell types. They undergo symmetric or asymmetric cell division into two daughter cells. In symmetric cell division, both daughter cells are also stem cells. In asymmetric division, a stem cell produces one stem cell and one specialized cell. NSCs primarily differentiate ...
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