FOXP2 (Forkhead bOX 2) is the first gene implicated in speech and language, and was firstly characterised through investigations in a large pedigree called the KE family. It is located on human chromosome 7q31 and encodes a 715 amino acid protein. The speech and language problems (i.e. developmental verbal dyspraxia – DVD) observed in the KE family occur due to the R553H missense mutation, which yields an arginine-to-histidine substitution in the DNA-binding domain of the FOXP2 protein. Interestingly, disruption of Foxp2 in songbirds and mice has been found to cause inaccurate vocal imitation and altered ultrasonic vocalization, respectively. Multiple studies have also demonstrated the importance of Foxp2 in neural development as well as synaptic plasticity. For instance, heterozygous R552H mice display abnormal synaptic plasticity in striatal and cerebellar neural circuits. Implications of the Foxp subfamily in neural development include, amongst others, Foxp1 role in promoting midbrain identity in vitro, and Foxp2 role in controlling neurogenesis during embryonic cortical development. Nevertheless, the mechanism that underpins these physiological functions remains unclear. Chiu and colleagues in their paper provide extraordinary evidence to support a prominent role of Foxp2 in the neuronal development of embryonic forebrain.
Chiu and colleagues (2014) used neural progenitor cells isolated from the forebrain of E14.5 mouse embryos to investigate these roles of Foxp2. To test whether Foxp2 promotes neuronal differentiation the authors performed gain-of-function experiments with Cerebral cortex (CTX) progenitors (as Foxp2 expression is low in the CTX), and loss-of-function experiments with Ganglionic eminence (GE) progenitors (as ...
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...d whether they are negatively regulated by Foxp2 as well in order to provide an overall picture of Foxp2 role in the MGE. Foxp2 inhibits Shh pathway in the MGE, thus suppressing MGE-derived interneurons. This raises the question of how Foxp2 inhibits Shh as the authors have not demonstrated any interactions between Foxp2 and NKX2-1 (induced by Shh), a crucial transcription factor required for the generation of MGE-derived neurons.
Excitingly, this study seeks to link Foxp2 role in neuronal differentiation and neuronal subtype specification with the development of vocal behaviours. Even more excitingly, this study provides a new perspective for the pathogenesis of schizophrenia as interneuron deficits have been found in schizophrenia patients; thus, Foxp2 disruption may be responsible for these deficits and consequently responsible for this neuropsychiatric disorder.
Tsuang, M. T., Faraone, S. V., & Glatt, S. J. (2011). Schizophrenia. New York: Oxford University Press.
Percy, A. K. (1999). Inherited neurodegenerative disease: The evolution of our thinking. Journal of Child Neurology, 14(4), 256-62. Retrieved from
...e in the brain to deliver electrical stimulation to targeted areas that control movement (mayoclinic.com, 2013).
The neurodevelopmental Basis of Schizophrenia. Austin, TX: Landes Co.
The MECP2 gene makes a protein, also called MECP2, believed to play a pivotal role in silencing, turning off or regulating the activity of other genes. The MECP2 mutation (change in the gene) causes the turn-off/regulatory mechanism to fail, allowing other genes to function abnormally(Rett Syndrome - NORD). Rett syndrome is a genetic disorder of developmental failure of brain maturation. This is thought to occur when subsets of neurons and their connections are disrupted during a dynamic phase of brain development. This deviation occurs at the end of pregnancy or in the first few months of life during the critical phases of synapse development. How mutations in MeCP2 lead to Retts is not well understood but is the focus of intense research.
The dominance of recent research data points to either genetic or possibly prenatal factors as a likely explanation for the condition. Interest focuses on chromosomes, genes, blood levels, and hormones. Secretin is a hormone found to improve the language and cognitive abilities in autistic childr...
Chen, S., Sayana, P., Zhang, X., Le, W. (2013). Genetics of amyotrophic lateral sclerosis: and update. Molecular Neurodegeneration 8, 1-15
Encyclopedia of Stem Cell Research.
Wood, Frank B., and Elena L. Grigorenko. “Emerging Issues in the Genetics of Dyslexia: A
The children that are affected by this disability have delayed development of speech and language, along with serious intellectual disability. With FXS come various amounts of other issues for children and adults, which include, difficulty-paying attention, which can lead to attention deficit disorder (ADD), showing features of the autism spectrum and possibly having reoccurring seizures (Bagni, Tassone, Neri & Hagerman 2012). FXS is caused by mutations in the FMR1 gene, which is located on the X chromosome, therefore causing a malfunction in expressing the fragile X mental retardation protein that is vital in normal neural development (Bagni et al., 2012). “FXS is the most frequent form of inherited intellectual disability and is also linked to other neurologic and psychiatric disorders” (Bagni et al. 2012...
The symptoms of NF2 includes continuous ringing in the ears or hearing loss, “tumors along the eighth cranial nerve” (the nerve responsible for hearing), “cataracts at a young age”, tumors located in the brain and/or along the spinal cord (causing numbness), balancing problems, or the muscles literally waste away (National Human Genome Research Institute, 2016). When a mutation occurs in the gene NF2, Neurofibromatosis Type 2 takes place. The gene NF2 is the location of a code named merlin, or schwannomin, that’s function is currently unknown but thought to be “involved in controlling cell movement, cell shape, and communication between cells” as well as “insulate nerve cells” (Genetics Home Reference, 2012).
The Phonological Deficit and Magnocellular theory are two of the most dominant theories in dyslexic research. Various theories have been suggested to explain the nature and origin of dyslexia, however, they often served as additional support for either the phonological or magnocellular theories. The Double Deficit theory suggested that dyslexic symptoms were the result of speed-processing (7). The Genomic theory posed that dyslexia was a highly heritable disorder that can be localized to a specific genetic component, Finally, the Cerebellar Deficit theory suggested that dyslexia was the result of an abnormal cerebellum exist (2). With the constant debate of the biological nature versus the cognitive natur...
The FOXP2 gene sequence is involved in the development of speech, it helps us to enunciate words properly. People who have mutations in the gene cannot make the correct facial movements needed for normal human speech. Alterations of where and when the FOXP2 gene is produced could explain the complexity of the human language. ASPM (Abnormal Spindle-like Microcephaly Associated) is a gene that controls brain size. A mutation in the ASPM gene leads to a condition known as microcephaly which causes a reduced brain size that normally is around 70% less than the average brain. The ASPM gene encodes protein that are necessary in the development of neuroblasts, which has a direct influence on the number of neurons in the brain. Both of these genes help us to have a better understanding of what makes us different from chimpanzees. If a mutation in this gene happens, the individual has a problem. The main difference between the two is, one involves a function in the brain (FOXP2) and the other involves brain size (ASPM) . Due to positive selection both of these genes have evolved in humans, although they evolved at different
...e in the neurodevelopment cycle, such as increased neuronal dysfunction with decreased connectivity and increases in loss of neuropril and extrinsic factor like substance abuse, developmental stress, relationship problem(Elder, Evans and Nizette, 2007).