Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion

Abstract

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 in skull shaping and bone remodeling. Selective ablation of in cartilage disrupted pup vocalizations in a similar way to that of global 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.

DRD2andFOXP2are implicated in the associations between computerized device use and psychiatric disorders

“…45 Nevertheless, FOXP2 is consistently implicated in the human ability to communicate via complex speech. 37 Additionally, we uncovered multiple genetically correlated traits shared between ADHD and PhoneUse in the combined and sex-stratified cohorts, including "age at first sexual intercourse" and "risk taking." While these traits were detected by the PGC ADHD GWAS of both sexes combined, 13 the connection to PhoneUse is perhaps best explored in the sex-stratified cohorts.…”

“…The shared genetic architecture of these traits was investigated using genome-wide data considering both Table S13); in the PhoneUse GWAS, 6 genomic risk loci were identified, representing 6 individual significant variants (LD r 2 <0.1; Table S14). There was no overlap in genomic risk loci or individual significant variants between ADHD and PhoneUse; however, individual significant loci from both GWAS map to genes involved in fear recognition/consolidation (Sortilin Related VPS10 Domain Containing Receptor 3 (SORCS3) in ADHD 34 and Hypocretin Receptor 2 (HCRTR2) 35 in PhoneUse) and language/speech development/impairment (Semaphorin 6D (SEMA6D) in ADHD 36 and forkhead box transcription factor (FOXP2) in ADHD and PhoneUse; 37 Tables S13 and S14). FOXP2 was the only gene-based genome-wide significant result in both ADHD (p=9.32x10 -7 ) and PhoneUse (p=9.00x10 -11 ).…”

Whole-Genome Association Analyses of Sleep-disordered Breathing Phenotypes in the NHLBI TOPMed Program

“…FOXP2 is also expressed in brainstem respiratory areas including the pre-Bötzinger complex (which is essential for respiratory rhythmogenesis) and impacts airway morphology [ 107,108 ]. Two lysine demethylases (KDM4B and KDM6B) were also identified.…”

The promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MER41 primate-specific endogenous retrovirus: an evolutionary connection between immunity and cognition

“…FOXP2, a TF abundantly expressed in cortical neurons, is involved in the emergence of human speech (Fisher and Scharff, 2009;Scharff and Petri, 2011;Vernes et al, 2011;Xu et al, 2018 (Sin et al, 2015;Wang et al, 2003). However, a recent work established a short list of TFs that bind FOXP2 and are likely to form heterodimers that regulate FOXP2 availability and/or DNA binding properties in neurons (Estruch et al, 2018).…”