FOXP2 and language alterations in psychiatric pathology / FOXP2 and language alterations in psychiatric pathology

Abstract 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.

Resumen Antecedentes Desde los primeros reportes del lingüista Noam Chomsky ha quedado claro que el desarrollo del lenguaje tiene un importante componente genético. Diversos reportes en familias han mostrado la relación entre los trastornos del lenguaje y ciertos marcadores genéticos. El gen FOXP2 ha sido una pieza fundamental para entender el desarrollo del lenguaje. Se trata de un gen que codifica para un factor de transcripción con un dominio forkhead de unión al DNA y que participa en la regulación de la expresión de un gran número de genes durante el desarrollo embrionario de estructuras neuronales fundamentales para el desarrollo del habla y el lenguaje. Objetivo Presentar un panorama actualizado de la relación del gen FOXP2 en las alteraciones del lenguaje en la patología psiquiátrica. Método Revisión narrativa de la información reportada en diversas bases de datos sobre los recientes avances que soportan la participación genética en las alteraciones del lenguaje presentes en enfermedades psiquiátricas. Resultados Actualización del contenido relacionado con el gen FOXP2 y su participación en las alteraciones del lenguaje en las enfermedades psiquiátricas. Discusión y conclusión Los avances en el estudio genético de las alteraciones del lenguaje en la patología psiquiátrica abren nuevos caminos de investigación que permiten explorar cómo surgió y cómo ha evolucionado el lenguaje, así como para llevar a cabo estudios comparativos sobre la estructura y el funcionamiento de genes para aproximarse al entendimiento de esta compleja característica que nos hace humanos.

Decoding the biology of language and its implications in language acquisition

Associating human genetic makeup with the faculty of language has long been a goal for biolinguistics. This stimulated theidea that language is attributed to genes and language disabilities are caused by genetic mutations. However, application ofgenetic knowledge on language intervention is still a gap in the existing literature. In an effort to bridge this gap, this articlepresents an account of genetic and neural associations of language and synthesizes the genetic, neural, epigenetic andenvironmental facets involved in language. In addition to describing the association of genes with language, the neural andepigenetic aspects of language are also explored. Further, the environmental aspects of language such as language input,emotion and cognition are also traced back to gene expressions. Therefore, effective language intervention for languagelearning difficulties must offer genetics-informed solutions, both linguistic and medical.

FOXP in Tetrapoda: Intrinsically Disordered Regions, Short Linear Motifs and their evolutionary significance

Abstract The FOXP subfamily is probably the most extensively characterized subfamily of the forkhead superfamily, playing important roles in development and homeostasis in vertebrates. Intrinsically disorder protein regions (IDRs) are protein segments that exhibit multiple physical interactions and play critical roles in various biological processes, including regulation and signaling. IDRs in proteins may play an important role in the evolvability of genetic systems. In this study, we analyzed 77 orthologous FOXP genes/proteins from Tetrapoda, regarding protein disorder content and evolutionary rate. We also predicted the number and type of short linear motifs (SLIMs) in the IDRs. Similar levels of protein disorder (approximately 70%) were found for FOXP1, FOXP2, and FOXP4. However, for FOXP3, which is shorter in length and has a more specific function, the disordered content was lower (30%). Mammals showed higher protein disorders for FOXP1 and FOXP4 than non-mammals. Specific analyses related to linear motifs in the four genes showed also a clear differentiation between FOXPs in mammals and non-mammals. We predicted for the first time the role of IDRs and SLIMs in the FOXP gene family associated with possible adaptive novelties within Tetrapoda. For instance, we found gain and loss of important phosphorylation sites in the Homo sapiens FOXP2 IDR regions, with possible implication for the evolution of human speech.

Tetramethylpyrazine protects learning memory of hypoxichypoxia rats through interfering expression of GABA receptor and FOXP2 / 中国药理学通报

Aim To examine the influence of tetramethylpyrazine on learning and memory function of hypoxic hypoxia rats, and the expression of gamma aminobutyric acid(GABA) receptor and forkhead box P2(FOXP2) in hippocampus of rats.Methods A total of 120 Sprague Dawley rats were randomly divided into low hypoxic hypoxia and high hypoxic hypoxia groups, then according to different time points every group was divided into 1 d, 3 d, 7 d 15 d, 30 d group, with 12 rats per each group.Experiment group and the control group were treated with tetramethylpyrazine and 0.9% normal saline, respectively.The hypoxic hypoxia environment was achieved by putting the rats in a hypobaric chamber at a simulated altitude of 5 500 meters for different days.The capabilities of learning and memory of rats were detected by Morris water maze test.The expression of GABA receptor and FOXP2 protein in hippocampus of rat was determined by Western blot.Results ① Morris water maze test showed that the total distance of rats in the simulated hypobaric hypoxia control group was longer than that in the tetramethylpyrazine group(P0.05);however,GABAB1 receptor and FOXP2 protein rose from the third day(P<0.05).The expression of GABAAα1 receptor and FOXP2 protein expression were correlated to total distance of Morris water maze in the control group(r=-0.738, P<0.05;r=-0.693, P<0.05), and the expression of GABAB1 receptor was correlated with FOXP2 protein level(r=0.834, P<0.05).Conclusion The simulated high-altitude hypobaric hypoxia can decrease the learning and memory abilities of rats, which may be ameliorated by tetramethylpyrazine intervention, and this effect might be related to the increase of GABAB1R receptor and FOXP2 expression in hippocampus of rats.

Genetic studies on speech and language disorders / 동물의과학연구지

Speech and language are uniquely human-specific traits that have contributed to humans becoming the predominant species on earth from an evolutionary perspective. Disruptions in human speech and language function may result in diverse disorders, including stuttering, aphasia, articulation disorder, spasmodic dysphonia, verbal dyspraxia, dyslexia, and specific language impairment (SLI). These disorders often cluster within a family, and this clustering strongly supports the hypothesis that genes are involved in human speech and language functions. For several decades, multiple genetic studies, including linkage analysis and genomewide association studies, were performed in an effort to link a causative gene to each of these disorders, and several genetic studies revealed associations between mutations in specific genes and disorders such as stuttering, verbal dyspraxia, and SLI. One notable genetic discovery came from studies on stuttering in consanguineous Pakistani families; these studies suggested that mutations in lysosomal enzyme-targeting pathway genes (GNPTAB, GNPTG, and NAPGA) are associated with non-syndromic persistent stuttering. Another successful study identified FOXP2 in a Caucasian family affected by verbal dyspraxia. Furthermore, an abnormal ultrasonic vocalization pattern (USV) was observed in knock-in (KI) and humanized mouse models carrying mutations in the FOXP2 gene. Although studies have increased our understanding of the genetic causes of speech and language disorders, these genes can only explain a small fraction of all disorders in patients. In this paper, we summarize recent advances and future challenges in an effort to reveal the genetic causes of speech and language disorders in animal models.