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 ...
... middle of paper ...
...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
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.
...ember 25). The biological basis of antipsychotic response in schizophrenia. Journal of Psychopharmacology, 0, 1-12. DOI: 10.1177/0269881109106959
Chen, S., Sayana, P., Zhang, X., Le, W. (2013). Genetics of amyotrophic lateral sclerosis: and update. Molecular Neurodegeneration 8, 1-15
Emerging evidence implicates microglial play critical roles to the CNS development of the brain. Microglial are unique population arise from immature yolk-sac macrophages that migrate and colonize the developing brain (Ginhoux et al., 2010; Ransohoff and Cardona, 2010). Interestingly, microglial (or their precursor cells) are selectively integrating into proliferative neurogenic zone of the proliferation and regulating the size of neural precursor cell pool via phagocytose neural precursor cell upon completion of neurogenesis(Cunningham et al., 2013). Also, colonization of microglia in the developing brain almost concurs temporally with brain vascularisation, neuroepithelial-radial glia transformation, neuronal migration, and myelination. Recent advent of transgenic technology and pharmacology allowed the role of microglia during development and their correlation with neural development disorder to be investigated extensively. For instance, pharmacologically knockout or inactivation of embryonic microglia resulted in increases of neural precursor cells pool (Cunningham et al., 2013). Similar phenomenons were also observed in genetically knockout of microglial in mice. Colony stimulating factor 1R-deficient (Csf1r−/−) mice w...
Schizophrenia is one of the most misdiagnosed illnesses of all time. Its characteristics of identification – hallucinations, delusions, lack of body control, etc. - often cause it to be identified as depression or post-traumatic stress disorder (PTSD). Doctors and scientists still debate the major cause of schizophrenia. Through research it is carefully observed that genetic factors play a larger role in the cause of schizophrenia than environmental factors.
Biological connections to schizophrenia are not exclusively genes or environment, combination of genes and environment causes schizophrenia (Glick, 2005). Nature’s focus of life is gene electives and nurture is environmental causing direct influence to bump traits, environment and innate potential defining reality in schizophrenia (Glick, 2005). If both genes and environment are correct schizophrenia turns on and each contributes 100% (Glick, 2005). Psychologist cannot account for a single cause of schizophrenia; results from case studies leave multiple genetic factors, psychological assaults, environmental, and hormonal causes that affect brain chemistry (Lifespan, 2009).
National Library of Medicine, National Institute of Health. Schizophrenia. 31 Jan 2013. Web. 15 May 2014
While a phenotype as multifaceted as human language is certainly polygenic, FOXP2 is distinct in being linked to grammar. Because genes enabling cognitive faculties are often implicated in pathology, when the famous “KE” family displayed mutated alleles of FOXP2 resulting in dyspraxia, a motor speech disorder, it suggested that language deficiencies resulted from mutated gene expression in the brain (Spiteri et. al 2007). Indeed, FOXP2 is a potent transcription regulator, transcribing proteins that form complex neuronal networks in the brain’s computational modules, developing remarkable propensity for language (Spiteri et. al 2007).
Figure 4.1 depicts the macro section of a mouse embryo, the Alcian Blue stain indicates that there is connective tissue present. The Nasal cartilages is supposedly made up of Hyaline cartilage, however the staining method and its appearance, is hinted towards elastic cartilage. Although not visible or past the visible stage, Neural stem cells would have been present for the brain development, alongside Mesenchymal stem cells for cartilage and bone development (Alcian Blue stain).
Another important interaction is with Bax, a protein in the Bcl-2 family, that is important in apoptotic pathways. PrPC is known to inhibit Bax activity, preventing apoptosis in fetal neurons.1 Other proteins that are known to interact with PrPC include, but are not limited to, the Grb2 signal transduction adapter protein, TREK-1 potassium channel, tubulin, N-Cell adhesion molecule, and synapsin 1b, which is involved in synaptic vesicle trafficking.1 Because of its broad physiological cellular involvement, PrPC has the potential to influence many cellular functions. Although there have been somewhat mixed results, some PrPC knockout mice have shown normal development, followed by neuronal decline, due to a lack of the Prnp
1991). In addition, brain-derived neurotrophic factor, which is released in an activity-dependent manner and important for synaptic plasticity, activates CK2 in a concentration-dependent manner (Blanquet 1998).
There exist many theories and studies on the formation and evolution of language. FOXP, Forkhead box protein, is generally responsible for the development of speech and language for humans and other mammals and species as well. The purpose for this paper is to address the function, discovery, and evolution of the FOXP2 gene.
Both NT-3 and BDNF equally promote neurite growth whereas, NT-3 is also involved promoting synapse formation in vitro. I intend to study the SGN regenerative effect of intracochlear perfusion of NT-3 on noise exposed mouse. Similarly, CNTF is found in the organ of corti and it was found that CNTF expression goes down in deafened rats at about the same time as SGNs start to die. It was show in retinal ganglion cells that CNTF can promote regeneration. This shows that apart from neuronal survival CNTF could also promote