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Autism, as a neurodevelopmental disorder, has become an important public health issue worldwide. The mechanisms by which DNA methylation regulates gene expression contributing to autism are complex and elaborate. As a non-invasive, highly accurate prenatal diagnosis, DNA methylation screening can be used to detect whether the fetus may be at risk for autism. However, the results of this approach require a professional bioinformatics analysis, and the diagnosis cannot be directly confirmed. Therefore, DNA methylation screening is often used as an adjunct to prenatal diagnosis rather than the only diagnostic basis. In practice, doctors will make a comprehensive judgment based on the results of DNA methylation screening, combined with other prenatal diagnosis methods, such as gene sequencing. Some studies have found a large number of DNA methylation abnormalities in the autistic brain, especially in genes related to neurodevelopment. These aberrant DNA methylation states may contribute to autism by affecting the expression of these genes, which in turn affects neuronal function and behavior. This study aimed to investigate the role of DNA methylation in autism and the application of detection techniques.

Copy number variants (CNVs) found in individuals with communication deficits provide a valuable window to the genetic causes of problems with language and, more generally, to the genetic foundation of the human-specific ability to learn and use languages. This paper reports on the language and communication problems of a patient with a microduplication in 22q11.23 and a microdeletion in 7q31.1-q1.33 encompassing FOXP2. The proband exhibits severe speech problems and moderate comprehension deficits, whereas her pragmatic abilities are a relative strength, as she uses gestures quite competently to compensate for her expressive issues. This profile is compatible with the deficiencies found in patients with similar CNVs, particularly with people bearing microdeletions in 7q31.1-q31.33. [ABSTRACT FROM AUTHOR]

Background & Objective: The aim of this study was to investigate the effect of saffron extract on the embryo development of mice. Materials & Methods: Pregnant NMRI mice were randomized into control and treatment groups at 25, 50, and 100 mg/kg saffron doses. Saffron extract was administered to mice by gavage on days 7-12 of pregnancy. On the 17th day of pregnancy, the embryos were removed from the uterus and their weight and height measured. Moreover, their brain tissue has been evaluated histologically. Subsequently, the expression of the Foxp2 and Ascl1 genes in the brain tissue was assessed using the real-time PCR method. Results: All embryos were aborted in mothers that received 100 mg/kg of saffron. At dose 50 mg/kg, only embryos of a mother reached the end of pregnancy. Embryos treated with 25 mg/kg saffron were significantly heavier than controls (P

Objective: It was aimed to investigate the role of the forkhead box protein P2 (FOXP2) gene in the cause of specific learning disorder (SLD) with the next-generation sequencing method. Material and methods: The study included 52 children diagnosed with SLD and 46 children as control between the ages of 6–12 years. Interview Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifelong Version in Turkish, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-Based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders, Specific Learning Disability Test Battery were applied to all participants. The FOXP2 gene was screened by the next-generation sequencing (NGS) method in all participants. Results: A total of 17 variations were detected in the FOXP2 gene in participants. The number and diversity of variations were higher in the patient group. In the patient group, c.1914 + 8A>T heterozygous variation and three different types of heterozygous variation (13insT, 13delT and 4dup) in the c.1770 region were detected. It was found that the detected variations showed significant relationships with the reading phenotypes determined by the test battery. Conclusion: It was found that FOXP2 variations were seen more frequently in the patient group. Some of the detected variations might be related to the clinical phenotype of SLD and variations found in previous studies from different countries were not seen in Turkish population. Our study is the first to evaluate the role of FOXP2 gene variations in children with SLD in Turkish population, and novel variations in the related gene were detected. [ABSTRACT FROM AUTHOR]

Language does not leave a fossil we can put under a microscope; there is no living witness to its origin, early functions and its stages of evolution. Thus, the study of language origin and development is based mostly on speculations or guesses we need to take in order to see the big picture and to try to solve some of the greatest mysteries of human history - a jigsaw puzzle made out of millions of pieces scattered around the world. So as to fully explore and grasp the notion of language, it appears fundamental to start from dissecting and putting under a microscope all components, properties, processes and manifestations of language, a selection of which has been offered throughout this paper. There are very few certainties in this field; however, it has been established that certain properties and aspects of language had to coincide for it to originate, viz. the descent of the larynx, the growth and reshaping of the brain and skull, changes of speech apparatus and finally the emergence of syntax. First though, a collective shift in thinking must have occurred, generating the mental readiness for language capacity and the need to expand the existing communication system. Once the requirement was established, human anatomy must have eventually followed. Consequently, the process of externalization was activated, engineered by the consistent and coherent socio-cultural transmission, which redesigned human interaction, communication and social organisation. Scientific evidence, presented in this paper, suggests that language could not have emerged as a result of a sudden shift, on the contrary, it must have been a result of complex processes, mental and biological on one level and social and psychological on the other. [ABSTRACT FROM AUTHOR]

FOXP2 has been identified as a gene related to speech in humans, based on rare mutations that yield significant impairments in speech at the level of both motor performance and language comprehension. Disruptions of the murine orthologue Foxp2 in mouse pups have been shown to interfere with production of ultrasonic vocalizations (USVs). However, it remains unclear which structures are responsible for these deficits. Here, we show that conditional knockout mice with selective Foxp2 deletions targeting the cerebral cortex, striatum or cerebellum, three key sites of motor control with robust neural gene expression, do not recapture the profile of pup USV deficits observed in mice with global disruptions of this gene. Moreover, we observed that global Foxp2 knockout pups show substantive reductions in USV production as well as an overproduction of short broadband noise "clicks", which was not present in the brain region-specific knockouts. These data indicate that deficits of Foxp2 expression in the cortex, striatum or cerebellum cannot solely explain the disrupted vocalization behaviours in global Foxp2 knockouts. Our findings raise the possibility that the impact of Foxp2 disruption on USV is mediated at least in part by effects of this gene on the anatomical prerequisites for vocalizing. [ABSTRACT FROM AUTHOR]

The protein-coding gene FoxP2 (fork head box protein P2) plays a major role in communication and evolutionary changes. The present study carried out a comprehensive codon usage bias analysis in the FoxP2 gene among a diverse group of animals including fishes, birds, reptiles, and mammals. We observed that in the genome of fishes for the FoxP2 gene, codons ending with C or G were most frequently used, while in birds, reptiles, and mammals, codons ending with T or A were most frequently used. A higher ENC value was observed for the FoxP2 gene indicating a lower CUB. Parity role two-bias plots suggested that apart from mutation pressure, other factors such as natural selection might have influenced the CUB. The frequency distribution of the ENC observed and ENC expected ratio revealed that mutation pressure plays a key role in the patterns of codon usage of FoxP2. Besides, correspondence analysis exposed the composition of the nucleobase under mutation bias affects the codon usage of the FoxP2 gene. However, neutrality plots revealed the major role of natural selection over mutation pressure in the CUB of FoxP2. In addition, the codon usage patterns for FoxP2 among the selected genomes suggested that nature has favored nearly all the synonymous codons for encoding the corresponding amino acid. The uniform usage of 12 synonymous codons for FoxP2 was observed among the species of birds. The amino acid usage frequency for FoxP2 revealed that the amino acids Leucine, Glutamine, and Serine were predominant over other amino acids among all the species of fishes, birds, reptiles, and mammals.

Background. From the first reports of the linguist Noam Chomsky it has become clear that the development of language has an important genetic component. Several reports in families have shown the relationship between language disorders and genetic polymorphisms. The FOXP2 gene has been a fundamental piece for the understanding of language development. This gene codes for a transcription factor containing a forkhead domain of DNA binding and participates in the regulation of the expression of a large number of genes involved in the embryonic development of fundamental neuronal structures needed for the development of speech and language. Objective. To present an updated view of the relationship between FOXP2 and language alterations in psychiatric pathology. Method. Narrative review of information reported in databases on the recent advances supporting genetic participation in language disorders of psychiatric illness. Results. Update of content related to FOXP2 and its participation in language alterations in psychiatric diseases. Discussion and conclusion. Advances in the genetic study of language disorders in psychiatric pathology open up new avenues of investigation that allow us to explore how language emerged and how it evolved, as well as to carry out comparative studies on the structure and functioning of genes to approach the understanding of this complex characteristic that makes us human. [ABSTRACT FROM AUTHOR]

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant entity characterized by eyelid malformations and caused by mutations in the forkhead box L2 (FOXL2) gene. Clinical and genetic analyses of large cohorts of BPES patients from different ethnic origins are important for a better characterization of FOXL2 mutational landscape. The purpose of this study is to describe the phenotypic features and the causal FOXL2 variants in a Mexican cohort of BPES patients. A total of 12 individuals with typical facial findings were included. Clinical evaluation included palpebral measurements and levator function assessment. The complete coding sequence of FOXL2 was amplified by PCR and subsequently analyzed by Sanger sequencing. A total of 11 distinct FOXL2 pathogenic variants were identified in our cohort (molecular diagnostic rate of 92%), including 5 novel mutations. Our results broaden the BPES-related mutational spectrum and supports considerable FOXL2 allelic heterogeneity in our population. • First molecular analysis of FOXL2 gene in Mexican cohort with BPES syndrome • 92% of all patients had heterozygous pathogenic variant. • Five novel mutations were identified. • Two changes identified may be associated to POF. [ABSTRACT FROM AUTHOR]

Protein–protein and protein–substrate interactions are critical to function and often depend on factors that are difficult to disentangle. Herein, a combined biochemical and biophysical approach, based on electrically switchable DNA biochips and single‐molecule mass analysis, was used to characterize the DNA binding and protein oligomerization of the transcription factor, forkhead box protein P2 (FOXP2). FOXP2 contains domains commonly involved in nucleic‐acid binding and protein oligomerization, such as a C2H2‐zinc finger (ZF), and a leucine zipper (LZ), whose roles in FOXP2 remain largely unknown. We found that the LZ mediates FOXP2 dimerization via coiled‐coil formation but also contributes to DNA binding. The ZF contributes to protein dimerization when the LZ coiled‐coil is intact, but it is not involved in DNA binding. The forkhead domain (FHD) is the key driver of DNA binding. Our data contributes to understanding the mechanisms behind the transcriptional activity of FOXP2. [ABSTRACT FROM AUTHOR]

Abstract The activation of peroxisome proliferator-activated receptor γ (PPAR-γ) has been shown to attenuate allergic airway inflammation (AAI). To gain better understanding of mechanisms underlying this effect, the impact of rosiglitazone (RSG), a PPAR-γ agonist, on CD4+ effector (Teff) and Foxp3-expressing regulatory (Treg) T cells in a mouse model of allergic asthma was studied. Furthermore, we investigated whether the activation of PPAR-γ may directly affect IL-4, IL-10 and IL-17 production by CD4+ T cells. RSG attenuated but did not prevent ovalbumin (OVA)-induced AAI, and this effect was PPAR-γ-dependent. RSG reduced but did not abolish the OVA-induced increase in the count of CD4+ Teff cells in the mediastinal lymph nodes (MLNs) and lungs, and this effect was PPAR-γ-dependent. RSG did not affect the absolute number of Treg cells in the MLNs and lungs of OVA-immunized mice. In vitro exposure of lung lymphocytes to RSG did not influence the percentage of IL-4-, IL-10- and IL-17-producing CD4+ T cells. Our results indicate that the impairment of clonal expansion of CD4+ Teff cells in the MLNs is involved in the anti-asthmatic properties of PPAR-γ agonists. Activation of PPAR-γ did not affect the recruitment of Treg cells to the MLNs and lungs nor did it induce their local generation. This indicates that Treg cells are not involved in producing the anti-asthmatic effect of PPAR-γ agonists. The results suggest that beneficial effects of PPAR-γ agonists in asthma treatment are not mediated through a direct inhibitory effect on IL-4, IL-10 and IL-17 production by CD4+ Teff cells. [ABSTRACT FROM AUTHOR]

FOXP proteins form a subfamily of evolutionarily conserved transcription factors involved in the development and functioning of several tissues, including the central nervous system. In humans, mutations in FOXP1 and FOXP2 have been implicated in cognitive deficits including intellectual disability and speech disorders. Drosophila exhibits a single ortholog, called FoxP, but due to a lack of characterized mutants, our understanding of the gene remains poor. Here we show that the dimerization property required for mammalian FOXP function is conserved in Drosophila. In flies, FoxP is enriched in the adult brain, showing strong expression in ~1000 neurons of cholinergic, glutamatergic and GABAergic nature. We generate Drosophila loss-of-function mutants and UAS-FoxP transgenic lines for ectopic expression, and use them to characterize FoxP function in the nervous system. At the cellular level, we demonstrate that Drosophila FoxP is required in larvae for synaptic morphogenesis at axonal terminals of the neuromuscular junction and for dendrite development of dorsal multidendritic sensory neurons. In the developing brain, we find that FoxP plays important roles in α-lobe mushroom body formation. Finally, at a behavioral level, we show that Drosophila FoxP is important for locomotion, habituation learning and social space behavior of adult flies. Our work shows that Drosophila FoxP is important for regulating several neurodevelopmental processes and behaviors that are related to human disease or vertebrate disease model phenotypes. This suggests a high degree of functional conservation with vertebrate FOXP orthologues and established flies as a model system for understanding FOXP related pathologies. [ABSTRACT FROM AUTHOR]

The virus switch from latency state to the lytic cycle lead to an increase incidence B malignancies when failure the immune system to control on B cells after reactivation of the virus. The aimed of this research is determination the seroprevalence of EBV and evaluate the role of EBV that may be related to chronic diseases by diagnosis of EBV VCA IgG, EBV VCA IgM in serum patients with EBV and detect the role of regulatory T cells in the regulation of immune response in positive EBV patient by measurement gene expression of transcription factor of FOXP3. The research consists of 79 samples infected with EBV and divided into 2 groups (31 Hodgkin lymphoma, 48 symptoms) and 41 healthy divided into 2 groups (24 seropositive and 17 control) after diagnosis of EBV VCA IgG, EBV VCA IgM by using ELISA assay. The results obtained that, The level of IgM was high prevalence in Symptoms group at a percentage (6.25%) while the absence of this antibody in other 3 groups at a rate (0.0%). as well as the elevated level of IgG in Seropositive at a rate (58.53%) while decline this antibody in symptoms group at ratio (41.66%). also, the mean of Foxp3 significantly increased in Hodgkin lymphoma (28.95±12.91) and insymptoms group(22.23±10.34)compared with other two groups. [ABSTRACT FROM AUTHOR]

Highlights • Associations between genetic variants in FOXP2 and language are inconsistent. • None of the previous associations replicated in our large schizophrenia sample. • Comprehensive analysis in a clinical family sample indicated no role for common FOXP2 variants in language. Abstract The FOXP2 gene is hypothesised to be involved in schizophrenia by affecting speech and language development. Associations between common single nucleotide polymorphisms (SNPs) in FOXP2 and language have been inconsistent. We tested five previously associated SNPs for association with language in the Western Australian Family Study of Schizophrenia (n = 709, including n = 333 with schizophrenia/spectrum disorder) and found no significant associations. When we included all common FOXP2 variants, one SNP (rs2189008) was nominally associated with language. This is the most comprehensive analysis to date and indicates that common variants in FOXP2 do not play a major role in speech and language development in a clinical family sample. [ABSTRACT FROM AUTHOR]

Heterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal development and impair motor skills. However, it is unknown if striatal excitatory/inhibitory balance is affected during development and if the imbalance persists into adulthood. We investigated the effect of reduced Foxp2 expression, via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor-mediated) and increases inhibitory (GABA receptor-mediated) currents in D1 dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced Foxp2 expression increases GAD67 expression, leading to both increased presynaptic content and release of GABA. Finally, pharmacological blockade of inhibitory activity in vivo partially rescues motor skill learning deficits in heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the regulation of striatal direct pathway activity through managing inhibitory drive. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (PE) is a multifactorial pregnancy disorder, with serious consequences for both the mother and the fetus. Despite intense studies, the pathophysiology of PE remains enigmatic. Previous studies suggested that Treg dysfunction is involved in the pathogenesis of PE. We hypothesized that functional variants of the FOXP3 gene might be associated with PE via dysregulation of Treg cells. Of the 276 subjects, we genotyped three variants of FOXP3 by PCR-RFLP and Tetra ARMS-PCR methods. The genotypic frequencies of rs2232365 were found to be protective from the development of PE under codominant [odds ratio (OR) 0.49, 95 percent confidence interval (CI) 0.28-0.87, p-value = 0.043], dominant [odds ratio (OR) 0.54, 95 percent confidence interval (CI) 0.32-0.94, p-value = 0.027] and over dominant [odds ratio (OR) 0.57, 95 percent confidence interval (CI) 0.35-0.92, p-value = 0.02] models. Moreover, the rs3761548 conferred a risk of PE in recessive model [odds ratio (OR) 2.05, 95 percent confidence interval (CI) 1.08-3.88, p-value = 0.025]. However, no mutation was detected in FOXP3 exon2 in any of the studied samples. Based on our results, thought that FOXP3 variants may be an important contributor for the progression of PE in Iranian women. [ABSTRACT FROM AUTHOR]

Fundamental human traits, such as language and bipedalism, are associated with a range of anatomical adaptations in craniofacial shaping and skeletal remodeling. However, it is unclear how such morphological features arose during hominin evolution. FOXP2 is a brain-expressed transcription factor implicated in a rare disorder involving speech apraxia and language impairments. Analysis of its evolutionary history suggests that this gene may have contributed to the emergence of proficient spoken language. In the present study, through analyses of skeleton-specific knockout mice, we identified roles of Foxp2 in skull shaping and bone remodeling. Selective ablation of Foxp2 in cartilage disrupted pup vocalizations in a similar way to that of global Foxp2 mutants, which may be due to pleiotropic effects on craniofacial morphogenesis. Our findings also indicate that Foxp2 helps to regulate strength and length of hind limbs and maintenance of joint cartilage and intervertebral discs, which are all anatomical features that are susceptible to adaptations for bipedal locomotion. In light of the known roles of Foxp2 in brain circuits that are important for motor skills and spoken language, we suggest that this gene may have been well placed to contribute to coevolution of neural and anatomical adaptations related to speech and bipedal locomotion. [ABSTRACT FROM AUTHOR]

As a transcription factor regulated by bone morphogenetic protein 2 (BMP2), Forkhead c2 (Foxc2) plays a pivot role in osteogenesis/odontogenesis. However, the role of Foxc2 and BMP2 in regulating osteo-/odontogenic differentiation and mineralization of stem cells from apical papilla (SCAP) is still uncertain. In this research, overexpression of Foxc2 gene significantly improved the proliferation of SCAP four days and eight days after transfection, but overexpression of both Foxc2 and BMP2 genes significantly inhibited the proliferation of SCAP eight days after transfection. RT-qPCR and western blot results indicated that SCAP-Foxc2-BMP2 significantly upregulated osteo-/odontogenic genes and proteins at most of the time points in SCAP after transfection. Moreover, SCAP-Foxc2-BMP2 formed notably more alkaline phosphatase-positive and alizarin red-positive mineralized nodules than other three group cells sixteen days after transfection. In conclusion, our findings revealed that Foxc2 and BMP2 synergistically promoted osteo-/odontogenic differentiation and mineralization of SCAP in vitro. [ABSTRACT FROM AUTHOR]

Background Hepatic gluconeogenesis plays an important role in regulating fasting plasma glucose levels and is a target of anti-diabetic drugs. Several kinds of iridoid glucosides exhibit hypoglycemic effect, whereas the mechanism was not clear. Aim of the study In this study, the effects of geniposide and gentiopicroside, two natural iridoid glucosides, on hepatic gluconeogenesis were investigated. Methods Glucose uptake assay, MTT assay, q-PCR, luciferase assay and western blot assay were performed to investigate the pharmacological effect of geniposide and gentiopicroside on human liver cell line L02. Thereby the fast blood glucose and intraperitoneal glucose tolerance were measured in high fat diet induced hyperglycemic mice after geniposide or gentiopicroside administration. Results The results showed that geniposide and gentiopicroside inhibited the transcription of G6PC and PEPCK in L02 cells and in mice. Additional experimental data indicated that these two compounds were able to inhibit the transcriptional activity of FOXO1 by inducing phosphorylation of AKT at Ser473. Furthermore, we found that these two compounds alleviated high fat diet induced hyperglycemia in mice. Conclusions Geniposide and gentiopicroside might reduce blood glucose and suppress hepatic gluconeogenesis by regulating the AKT-FOXO1 pathway, and the potential use of these two iridoid glucosides as anti-diabetic agents merits further in-depth exploration. [ABSTRACT FROM AUTHOR]

The forkhead box (Fox) gene family, one of the most important families of transcription factors, participates in various biological processes. However, Fox genes in Hymenoptera are still poorly known. In this study, 14 Fox genes were identified in the genome of Apis cerana. In addition, 16 (Apis mellifera), 13 (Apis dorsata), 16 (Apis florea), 17 (Bombus terrestris), 16 (Bombus impatiens), and 18 (Megachile rotundata) Fox genes were identified in their genomes, respectively. Phylogenetic analyses suggest that FoxA is absent in the genome of A. dorsata genome. Similarly, FoxG is missing in the genomes A. cerana and A. dorsata. Temporal expression profiles obtained by quantitative real-time PCR revealed that Fox genes have distinct expression patterns in A. cerana, especially for three genes ACSNU03719T0 (AcFoxN4), ACSNU05765T0 (AcFoxB), and ACSNU07465T0 (AcFoxL2), which displayed high expression at the egg stage. Tissue expression patterns showed that FoxJ1 is significantly higher in the antennae of A. cerana and A. mellifera compared to other tissues. These results may facilitate a better understanding of the potential physiological functions of the Fox gene family in A. cerana and provide valuable information for a comprehensive functional analysis of the Fox gene family in Hymenopterans. [ABSTRACT FROM AUTHOR]

In the present study, 21 forkhead box (Fox) genes were identified in Andrias davidianus, including 13 fulllength genes and eight partial sequences. Phylogenetic analysis showed that most were conserved in other investigated amphibians, whereas the Foxk1 gene was found exclusively in A. davidianus. Molecular evolution analysis indicated that most Fox genes underwent purifying selection, whereas two sites of the adFoxp4 gene showed positive selection and were located on the adFoxp4 protein surface. Expression profiles of all Fox genes identified were analysed in the hypothalamic-pituitary-gonad axis by reverse transcription-quantitative polymerase chain reaction. Eighteen genes exhibited sexually dimorphic expression (15 ovary-biased and three testis-biased genes), whereas two genes showed no difference between ovary and testis. Further investigation of 12 selected sexually dimorphic Fox genes showed changes in the expression profile of 11 genes in the ovary of larvae reared at high temperatures (28°C). The results of the present study provide information on Fox genes in an amphibian and suggest that they play key roles in sexual development and reproduction in A. davidianus. [ABSTRACT FROM AUTHOR]

Background: Forkhead box P3 (FOXP3) is a key gene in the immune system which also plays a role in tumor development. This study aims to explore the association of two FOXP3 polymorphisms (rs3761548 and rs3761549) with susceptibility to breast cancer (BC). Method: A case–control study was conducted, involving 560 patients and 583 healthy individuals from the Chinese Han population. The genotypes of FOXP3 polymorphisms were detected using the Sequenom MassARRAY method. The association between FOXP3 polymorphisms and BC risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (95% CIs) under six genetic models. False-positive report probability was utilized to examine whether the significant findings were noteworthy. Results: We observed that rs3761548 was associated with a higher BC risk in heterozygous, dominant, overdominant, and allele genetic models (CA vs CC: OR =1.32, P=0.031; CA/AA vs CC: OR =1.32, P=0.023; CA vs CC/AA: OR =1.29, P=0.042; A vs C: OR =1.26, P=0.029), whereas no significant association was found between rs3761549 and BC risk. In addition, CA, CA/AA genotype, and A allele of rs3761548 were related to larger tumor size, and the A allele was also correlated with a positive status of Her-2 in BC patients. Conclusion: Our study suggests that FOXP3 polymorphism rs3761548 is associated with BC susceptibility in the Chinese and may be involved in tumor progression. Future studies are needed to confirm the results in a larger population with more races. [ABSTRACT FROM AUTHOR]

Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in nonneuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression. However, to date, little is known about the regulation of FOXP2 or the genomic elements that control its expression. Using chromatin conformation capture (3C), we mapped the human FOXP2 locus to identify putative enhancer regions that engage in long-range interactions with the promoter of this gene. We demonstrate the ability of the identified enhancer regions to drive gene expression. We also show regulation of the FOXP2 promoter and enhancer regions by candidate regulators - FOXP family and TBR1 transcription factors. These data point to regulatory elements that may contribute to the temporal- or tissue-specific expression patterns of human FOXP2. Understanding the upstream regulatory pathways controlling FOXP2 expression will bring new insight into the molecular networks contributing to human language and related disorders. [ABSTRACT FROM AUTHOR]

Objective Ovarian cancer is one of the most serious disease in female reproductive system. Platinum is the first-line drug for the treatment of ovarian cancer, while the resistance of platinum drug in clinical hindered the relief ovarian cancer. Our previous study found that decreased FOXO3a might be a poor prognosis in human ovarian cancer. In this research, we study whether FOXO3a was involved in the mechanism of platinum drug resistance. Methods The CCK-8 and FACS analysis were used to monitor the survival of ovarian cancer, and the FOXO3a expression was detected by western-blot. Results We found that FOXO3a expression upregulated significantly in A2780 compared with A2780/DDP cells with the treatment of platinum. Moreover, overexpression of FOXO3a in ovarian cancer inversed the platinum resistance in ovarian cancer. Conclusion These observations reminded that the role of FOXO3a might be one of the critical mechanisms in developing platinum drug resistance in ovarian cancer. [ABSTRACT FROM AUTHOR]

Superantigens (SAgs) produced by Staphylococcus aureus at high concentrations induce proliferation of T cells bearing specific TCR Vb sequences and massive cytokinemia that cause toxic shock syndrome. However, the biological relevance of SAgs produced at very low concentrations during asymptomatic colonization or chronic infections is not understood. In this study, we demonstrate that suboptimal stimulation of human PBMCs with a low concentration (1 ng/ml) of staphylococcal enterotoxin C1, at which half-maximal T cell proliferation was observed, induced CD8+CD25+ T cells expressing markers related to regulatory T cells (Tregs), such as IFN-γ, IL-10, TGF-β, FOXP3, CD28, CTLA4, TNFR2, CD45RO, and HLA-DR. Importantly, these CD8+CD25+ T cells suppressed responder cell proliferation mediated in contact-dependent and soluble factor-dependent manners, involving galectin-1 and granzymes, respectively. In contrast, optimal stimulation of human PBMCs with a high concentration (1 mg/ml) of staphylococcal enterotoxin C1, at which maximal T cell proliferation was observed, also induced similar expression of markers related to Tregs, including FOXP3 in CD8+CD25+ cells, but these T cells were not functionally immunosuppressive. We further demonstrated that SAg-induced TCR Vb-restricted and MHC class II-restricted expansion of immunosuppressive CD8+CD25+ T cells is independent of CD4+ T cells. Our results suggest that the concentration of SAg strongly affects the functional characteristics of activated T cells, and low concentrations of SAg produced during asymptomatic colonization or chronic S. aureus infection induce immunosuppressive CD8+ Tregs, potentially promoting colonization, propagation, and invasion of S. aureus in the host. [ABSTRACT FROM AUTHOR]

Insulin and leptin resistance are highly involved in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Presently, no approved treatment is available. Actein is isolated from the rthizomes of Cimicifuga foetida, a triterpene glycoside, exhibiting important biological properties, such as anti-inflammatory, anti-cancer, and anti-oxidant activity. However, its effects on metabolic syndrome are poorly understood. The aims of the study were mainly to investigate the molecular mechanisms regulating insulin and leptin resistance, and lipogenic action of actein in high fat diet-fed mice. Our data indicated that actein-treated mice displayed lower body weight, epididymal and subcutaneous fat mass, as well as serum lipid levels. Also, improved insulin and leptin resistance were observed in actein-treated groups. Liver inflammation and fibrosis triggered by high fat diet were decreased for actein administration. Moreover, hepatic lipid accumulation was also reduced by actein along with reductions of hepatic de novo lipogenesis-linked signals in actein-treated rodents with high fat diet. High fat diet-induced activation of insulin receptor substrate 1/Forkhead box protein O1 (IRS1/FOXO1), Janus kinase 2 gene/signal transducer and activator of transcription (JAK2/STAT3) and Protein Kinase B/Glycogen synthase kinase 3 beta (AKT/GSK3β) pathways in liver was inhibited by actein, a potential mechanism by which hyperinsulinemia, hyperleptindemia and dyslipidemia were attenuated. Thus, the findings above might be of nutritional and therapeutic importance for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans. [ABSTRACT FROM AUTHOR]

Aims Osteosarcoma (OS) is the most common primary bone malignancy that affects adolescents. Although great attention has been paid to the diagnosis of and therapy for OS, the 5-year survival rate of patients with this disease remains poor. MicroRNAs are small non-coding RNAs involved in pathogenesis and progression of human malignancies. MiR-139 has been implicated in several human cancers. However, the role played by miR-139 in pathogenesis of human OS has remained largely unknown. Main methods Realtime PCR was used to detect the expression of miR-139. CCK-8, BrdU-ELISA and ApoTox-Glo™ Triplex assay was employed to detect the proliferation and apoptosis of osteosarcoma cells. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis. Key findings The expression of miR-139 was reduced while the expression of forkhead-box P2 (FOXP2) was induced in both OS tissue and cell lines. The reduced level of miR-139 was correlated with tumor size, clinical stage and distant metastasis. Overexpression of miR-139 inhibited the expression of FOXP2, which suppressed cell growth, but induced apoptosis. Further, we confirmed that FOXP2 was a direct target of miR-139 by luciferase reporter assay. Knockdown of FOXP2 resulted in reduced levels of cell proliferation, but increased levels of apoptosis in vitro. Significance These findings suggest that miR-139 plays a suppressive role in the regulation of OS cell proliferation and migration via directly targeting FOXP2, which might be a potential clinical diagnostic or predictive biomarker for human OS. [ABSTRACT FROM AUTHOR]

The arthropod mushroom bodies ( MB) are a higher order sensory integration centre. In insects, they play a central role in associative olfactory learning and memory. In Drosophila melanogaster (Dm), the highly ordered connectivity of heterogeneous MB neuron populations has been mapped using sophisticated molecular genetic and anatomical techniques. The MB-core subpopulation was recently shown to express the transcription factor FoxP with relevance for decision-making. Here, we report the development and adult distribution of a FoxP-expressing neuron population in the MB of honeybees (Apis mellifera, Am) using in situ hybridisation and a custom-made antiserum. We found the same expression pattern in adult bumblebees ( Bombus terrestris, Bt). We also designed a new Dm transgenic line that reports FoxP transcriptional activity in the MB-core region, clarifying previously conflicting data of two other reporter lines. Considering developmental, anatomical and molecular similarities, our data are consistent with the concept of deep homology of FoxP expression in neuron populations coding reinforcement-based learning and habit formation. [ABSTRACT FROM AUTHOR]

Bifidobacterium longum ( B. Longum ) is a common probiotic colonized in the human gut and against the development of chronic inflammation including inflammatory bowel disease (IBD). But the underlying mechanism remains unknown. The aim of this study was to evaluate the affection of B. longum on the methylation levels of forkhead box P3 (Foxp3) promoter. 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colitis rat models were treated with B. longum or medium, respectively. The genomic DNA of spleen peripheral blood mononuclear cells (PBMC) cells was extracted. After bisulphite treatment and pyrosequencing, the methylation levels of each CpG sites in the promoter of forkhead box protein P3 (Foxp3) were analyzed. B. Longum treatment changes the methylation level in Foxp3 promoter in TNBS-treated colitis rats, and significantly demethylates several CpG sites in Foxp3 promoter. The demethylation of Foxp3 promoter might be involved in the effectiveness of B. Longum treatment for IBD. Further research remains necessary to investigate the role of B. Longum in Foxp3 demethylation. Using B. Longum or its metabolic products is an option for further investigations on potential treatments for IBD. [ABSTRACT FROM AUTHOR]

Disruption of FOXP2 , a gene encoding a forkhead domain transcription factor, may cause a severe developmental disorder of verbal communication, especially vocalization. In insectivorous bats, accelerated evolution of FoxP2 supports a previously proposed hypothesis that this gene plays a role in sensorimotor coordination. In order to validate this hypothesis, it is necessary to examine the expression of FoxP2 in the relevant sensorimotor structures involved in echolocation behavior. Here, we present the detailed spatial expression pattern of FoxP2 in the mature brain of Rhinolophus ferrumequinum using immunohistochemistry. FoxP2 expression was found in many regions of the bat brain. The homologous pattern of FoxP2 expression in this bat argues for the role of the gene in motor-related circuits. In addition, FoxP2 was strongly expressed in many regions related to echolocation such as the inferior colliculus, superior colliculus, periaqueductal gray, paralemniscal nucleus, nuclei of the lateral lemniscus, parabrachial nucleus and ambiguous nucleus. Overall, our findings imply that FoxP2 plays an important role in echolocation. [ABSTRACT FROM AUTHOR]

The forkhead- box P2 (FOXP2) gene polymorphism has been reported to be involved in the susceptibility to schizophrenia; however, few studies have investigated the association between FOXP2 gene polymorphism and clinical symptoms in schizophrenia. This study investigated whether the FOXP2 gene was associated with the development and symptoms of schizophrenia in relatively genetically homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped in 1069 schizophrenia inpatients and 410 healthy controls using a case-control design. The patients' psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). We found no significant differences in the genotype and allele distributions between the patient and control groups. Interestingly, we found significant differences in PANSS total, positive symptom, and general psychopathology scores between genotypic subgroups in patients, with the higher score in patients with CC genotype than those with CT genotype (all p < 0.05). After adjusting demographic and clinical variables, the difference still remained significant for the PANSS positive symptom score and general psychopathology (both p < 0.05). Our findings suggest that the FOXP2 rs10447760 polymorphism may not contribute to the development of schizophrenia, but may contribute to the clinical symptoms of schizophrenia among Han Chinese. [ABSTRACT FROM AUTHOR]

The forkhead box subclass O (FoxO) family of proteins is a group of highly evolutionary conserved transcription factors that regulate various cellular processes and embryonic development. Dysregulated expressions of FOXO genes have been identified in numerous tumors and genetic disorders. The expression of FOXO/ Foxo, particularly FOXO4/ Foxo4 and FOXO6/ Foxo6, in the developing nervous system has not been fully characterized. Here, we identified zebrafish foxo4, foxo6a, and foxo6b homologs and demonstrated that all three genes were expressed in the developing nervous system. foxo4, foxo6a, and foxo6b displayed ubiquitous expression in the brain and later in distinct brain tissues. In addition, these three genes were expressed in different retinal layers in a time-dependent manner. Furthermore, the mRNA expression of all three genes was significantly downregulated after treatment with a selective PI3-kinase (PI3K) inhibitor, LY294002. Our results suggest that foxo4, foxo6a, and foxo6b play important roles in the developing brain and retina and that the transcriptional levels of these genes are regulated by PI3-kinase signaling. [ABSTRACT FROM AUTHOR]

The Forkhead transcription factor FOXP2 is implicated in speech perception and production. The avian homolog, FoxP21 contributes to song learning and production in birds. In human cell lines, transcriptional activity of FOXP2 requires homo-dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2 and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song control region in zebra finches. We now report on dimer- and oligomerization of zebra finch FoxPs and how this affects transcription. In cell lines and in the brain we identify homo- and hetero-dimers, and an oligomer composed of FoxP1/2/4. We further show that FoxP1/2 but not FoxP4 bind to the regulatory region of the target gene Contactin-associated protein-like 2 (CNTNAP2). In addition, we demonstrate that FoxP1/4 bind to the regulatory region of very low density lipoprotein receptor (VLDLR), as has been shown for FoxP2 previously. Interestingly, FoxP1/2/4 individually or in combinations regulate the promoters for SV40, zebra finch VLDLR and CNTNAP2 differentially. These data exemplify the potential for complex transcriptional regulation of FoxP1/2/4, highlighting the need for future functional studies dissecting their differential regulation in the brain. [ABSTRACT FROM AUTHOR]

Although the anatomical and physiological properties of subtypes of retinal ganglion cells (RGCs) have been extensively investigated, their molecular properties are still unclear. Here, we examined the expression patterns of FoxP2 in the retina of ferrets and mice. We found that FoxP2 was expressed in small subsets of neurons in the adult ferret retina. FoxP2-positive neurons in the ganglion cell layer were divided into two groups. Large FoxP2-positive neurons expressed Brn3a and were retrogradely labeled with cholera toxin subunit B injected into the optic nerve, indicating that they are RGCs. The soma size and the projection pattern of FoxP2-positive RGCs were consistent with those of X cells. Because we previously reported that FoxP2 was selectively expressed in X cells in the ferret lateral geniculate nucleus (LGN), our findings indicate that FoxP2 is specifically expressed in the parvocellular pathway from the retina to the LGN. Small FoxP2-positive neurons were positive for GAD65/67, suggesting that they are GABAergic amacrine cells. Most Foxp2-positive cells were RGCs in the adult mouse retina. Dendritic morphological analyses suggested that Foxp2-positive RGCs included direction-selective RGCs in mice. Thus, our findings suggest that FoxP2 is expressed in specific subtypes of RGCs in the retina of ferrets and mice. [ABSTRACT FROM AUTHOR]

Background Mutations in the gene encoding the transcription factor forkhead box P2 ( FOXP2 ) result in brain developmental abnormalities, including reduced gray matter in both human patients and rodent models and speech and language deficits. However, neither the region-specific function of FOXP2 in the brain, in particular the cerebellum, nor the effects of any posttranslational modifications of FOXP2 in the brain and disorders have been explored. Methods We characterized sumoylation of FOXP2 biochemically and analyzed the region-specific function and sumoylation of FOXP2 in the developing mouse cerebellum. Using in utero electroporation to manipulate the sumoylation state of FOXP2 as well as Foxp2 expression levels in Purkinje cells of the cerebellum in vivo, we reduced Foxp2 expression approximately 40% in the mouse cerebellum. Such a reduction approximates the haploinsufficiency observed in human patients who demonstrate speech and language impairments. Results We identified sumoylation of FOXP2 at K674 (K673 in mice) in the cerebellum of neonates. In vitro co-immunoprecipitation and in vivo colocalization experiments suggest that PIAS3 acts as the small ubiquitin-like modifier E3 ligase for FOXP2 sumoylation. This sumoylation modifies transcriptional regulation by FOXP2. We demonstrated that FOXP2 sumoylation is required for regulation of cerebellar motor function and vocal communication, likely through dendritic outgrowth and arborization of Purkinje cells in the mouse cerebellum. Conclusions Sumoylation of FOXP2 in neonatal mouse cerebellum regulates Purkinje cell development and motor functions and vocal communication, demonstrating evidence for sumoylation in regulating mammalian behaviors. [ABSTRACT FROM AUTHOR]

Syntactic language is a uniquely human accomplishment, and must therefore have evolved since the split of the hominins from the other great apes some six million years ago. I argue that there were three main phases. The first came about through the emergence of bipedalism, a distinctively hominin trait, which enhanced the capacity for manual communication by freeing the hands and opening a frontal stance. The second began with the emergence of the larger-brained genus Homo from around 2 million years ago. The increase in brain size may have been driven by the necessity for enhanced social cooperation, and the emergence of a more effective system for communicating propositional information. Many of the properties of language, including the use of arbitrary symbols, and the emergence of tense and other markers of time and place, may have been driven by the increased understanding of time, and the advantages gained by recording and communicating episodic events. In short, language acquired syntax. The final stage, unique to Homo sapiens, was the emergence of autonomous speech as the primary mode of communication, replacing earlier dependence on manual gesture. This may help explain the dominance of our species over other hominin species, and indeed over the planet

The article reflects on an article published in the 2014 issue of the periodical on the relation between FOXP2 with retinoic acid signaling pathways which helps in shaping the speech-related motor circuitry.

Background Mutations in FOXL2 are known to cause autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), variably associated with premature ovarian failure. In this study, we report results of mutational screening in a Czech and Slovak patient population with BPES. Design Case series. Participants Thirteen probands of Czech and one proband of Slovak origin with BPES and their available family members. Methods Sanger sequencing and multiplex ligation-dependent probe amplification in 14 probands with BPES. Targeted mutational screening in first-degree relatives. Main Outcome Measures Genetic characterization and phenotype evaluation in Czech and Slovak individuals with BPES and their family members. Results Eight different mutations were detected including three novel ones: c.5T>G; p.(Met2Arg), c.197C>A; p.(Ala66Glu) and c.701_702insTGCAGCCGCAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC; p.(Ala222_Ala234dup). In one family, the molecular genetic cause of disease was not identified by the methodology used. In 13 pedigrees, a negative family history suggested a de novo origin, which could be confirmed by targeted mutational screening in four families. One 62-year-old female with the c.663_692dup30 mutation had an atypical phenotype presenting as moderate ptosis compensated by frontalis muscle contraction, no epicanthus inversus and no premature ovarian failure. Conclusions The de novo mutation rate in FOXL2 is exceptionally high compared with other dominant disorders manifesting with an ocular phenotype. In cases reporting a negative family history, careful examination of both parents is important to exclude mild features of the BPES phenotype. [ABSTRACT FROM AUTHOR]

The article focuses on laminin subunit alpha-5 gene variants forkhead box protein C2 (FOXC2) and Fms-related tyrosine kinase 4 (FLT4) and their contribution to severity. Topics include FOXC2 and FLT4's role in causing lymphedema-distichiasis syndrome and Milroy disease (MD), expansion of phenotypes using indocyanine green fluorescence lymphography and magnetic resonance lymphangiography, and enhancement of lymphatics in MD patients through indocyanine green fluorescent lymphography imaging.

FOXP2 is altered in a variety of language disorders. We found reduced mRNA and protein expression of FOXP2 in frontal cortex area 8 in Pick's disease, and frontotemporal lobar degeneration-tau linked to P301L mutation presenting with language impairment in comparison with age-matched controls and cases with parkinsonian variant progressive supranuclear palsy. Foxp2 mRNA and protein are also reduced with disease progression in the somatosensory cortex in transgenic mice bearing the P301S mutation in MAPT when compared with wild-type littermates. Our findings support the presence of FOXP2 expression abnormalities in sporadic and familial frontotemporal degeneration tauopathies. [ABSTRACT FROM AUTHOR]

Development of proficient spoken language skills is disrupted by mutations of the FOXP2 transcription factor. A heterozygous missense mutation in the KE family causes speech apraxia, involving difficulty producing words with complex learned sequences of syllables. Manipulations in songbirds have helped to elucidate the role of this gene in vocal learning, but findings in non-human mammals have been limited or inconclusive. Here, we performed a systematic study of ultrasonic vocalizations (USVs) of adult male mice carrying the KE family mutation. Using novel statistical tools, we found that Foxp2 heterozygous mice did not have detectable changes in USV syllable acoustic structure, but produced shorter sequences and did not shift to more complex syntax in social contexts where wildtype animals did. Heterozygous mice also displayed a shift in the position of their rudimentary laryngeal motor cortex (LMC) layer-5 neurons. Our findings indicate that although mouse USVs are mostly innate, the underlying contributions of FoxP2 to sequencing of vocalizations are conserved with humans. [ABSTRACT FROM AUTHOR]

Granulosa cell tumors (GCTs) of the ovary are uncommon neoplasms, accounting for ∼5% of all malignant ovarian tumors. GCTs are a relatively homogeneous group of tumors, categorized into two distinct subtypes, juvenile GCT and adult GCT (AGCT), likely arising from a limited set of molecular events usually involving the disruption of pathways that regulate granulosa cell proliferation. In the present study, the presence of forkheadbox L2 (FOXL2) c.402C>G mutation was investigated in a series of 42 samples of primary and metastatic AGCT of the ovary. The samples consisted of 37 primary and 5 metastatic ovarian AGCTs from 37 patients. FOXL2 mutational status was evaluated using a pyrosequencing approach on 2.5-μm sections of formalin-fixed paraffin-embedded tissue. FOXL2 c.402C>G mutation was found in 33/37 (89.2%) primary AGCTs and in 4/5 (80.0%) metastases, with the molecular status of the metastases recapitulating that of the primary tumors (4 mutated cases and 1 wild-type case). Overall, FOXL2 mutation is present in the majority of primary and metastatic AGCTs, and could be used as a valid tool in the diagnosis of the disease and in cases of metastatic lesions from an unknown primary origin. Moreover the concordance of FOXL2 molecular status in primary and associated metastases suggests its early appearance and genomic stability in AGCT tumorigenesis. [ABSTRACT FROM AUTHOR]

Mutations of the transcription factor FOXP2 cause a severe speech and language disorder. In songbirds, FoxP2 is expressed in the medium spiny neurons (MSNs) of the avian basal ganglia song nucleus, Area X, which is crucial for song learning and adult song performance. Experimental downregulation of FoxP2 in Area X affects spine formation, prevents neuronal plasticity induced by social context and impairs song learning. Direct target genes of FoxP2 relevant for song learning and song production are unknown. Here we show that a lentivirally mediated FoxP2 knockdown in Area X of zebra finches downregulates the expression of VLDLR , one of the two reelin receptors. Zebra finch FoxP2 binds to the promoter of VLDLR and activates it, establishing VLDLR as a direct FoxP2 target. Consistent with these findings, VLDLR expression is co-regulated with FoxP2 as a consequence of adult singing and during song learning. We also demonstrate that knockdown of FoxP2 affects glutamatergic transmission at the corticostriatal MSN synapse. These data raise the possibility that the regulatory relationship between FoxP2 and VLDLR guides structural plasticity towards the subset of FoxP2-positive MSNs in an activity dependent manner via the reelin pathway. [ABSTRACT FROM AUTHOR]

In the mammalian telencephalon, part of the progenitor cells transition from multipolar to bipolar morphology as they invade the mantle zone. This associates with changing patterns of radial migration. However, the molecules implicated in these morphology transitions are not well known. In the present work, we analyzed the function of FoxP2 protein in this process during telencephalic development in vertebrates. We analyzed the expression of FoxP2 protein and its relation with cell morphology and migratory patterns in mouse and chicken developing striatum. We observed FoxP2 protein expressed in a gradient from the subventricular zone to the mantle layer in mice embryos. In the FoxP2 low domain cells showed multipolar migration. In the striatal mantle layer where FoxP2 protein expression is higher, cells showed locomoting migration and bipolar morphology. In contrast, FoxP2 showed a high and homogenous expression pattern in chicken striatum, thus bipolar morphology predominated. Elevation of FoxP2 in the striatal subventricular zone by in utero electroporation promoted bipolar morphology and impaired multipolar radial migration. In mouse cerebral cortex we obtained similar results. FoxP2 promotes transition from multipolar to bipolar morphology by means of gradiental expression in mouse striatum and cortex. Together these results indicate a role of FoxP2 differential expression in cell morphology control of the vertebrate telencephalon. [ABSTRACT FROM AUTHOR]

Much of our current knowledge regarding the association of FOXP2 with speech and language development comes from singleton and small family studies where a small number of rare variants have been identified. However, neither genome-wide nor gene-specific studies have provided evidence that common polymorphisms in the gene contribute to individual differences in language development in the general population. One explanation for this inconsistency is that previous studies have been limited to relatively small samples of individuals with low language abilities, using low density gene coverage. The current study examined the association between common variants in FOXP2 and a quantitative measure of language ability in a population-based cohort of European decent (n = 812). No significant associations were found for a panel of 13 SNPs that covered the coding region of FOXP2 and extended into the promoter region. Power analyses indicated we should have been able to detect a QTL variance of 0.02 for an associated allele with MAF of 0.2 or greater with 80% power. This suggests that, if a common variant associated with language ability in this gene does exist, it is likely of small effect. Our findings lead us to conclude that while genetic variants in FOXP2 may be significant for rare forms of language impairment, they do not contribute appreciably to individual variation in the normal range as found in the general population. [ABSTRACT FROM AUTHOR]