Pleiotropic function of Dlx5/6 in the development of mammalian vocal and auditory organs

Abstract

Acoustic communication, a cornerstone of social interactions in mammals, relies on both vocal (effector) and auditory (receptor) organs, which display remarkable morphological diversity across species. The molecular mechanisms supporting the coordinated diversification of effector and receptor systems along with the evolution of species-specific acoustic communication are still poorly understood. A plausible hypothesis is that common genetic pathways orchestrate the parallel morphogenesis of vocal and auditory structures. Here, we addressed this question by generating mutant mice with targeted inactivation of Dlx5/6 genes in the Sox10 lineage, which includes neural crest and otic placode derivatives that contribute to the formation of vocal tract and ear components. We show that Dlx5/6 inactivation led to simultaneous patterning defects in the outer, middle and inner ear and of the jaw, pharynx and larynx musculoskeletal systems. We further show that Dlx5/6 modulate the BMP signalling pathway in both pharyngeal arches and otic vesicle, revealing a common Dlx5/6-BMP axis acting concurrently within the Sox10 derivatives. These findings highlight a pleiotropic role of Dlx5/6 in vocal and auditory morphogenesis, thereby suggesting their contribution in the co-adaptation of effector and receptor organs and in the diversification of acoustic communication in mammals.Acoustic communication, a cornerstone of social interactions in mammals, relies on both vocal (effector) and auditory (receptor) organs, which display remarkable morphological diversity across species. The molecular mechanisms supporting the coordinated diversification of effector and receptor systems along with the evolution of species-specific acoustic communication are still poorly understood. A plausible hypothesis is that common genetic pathways orchestrate the parallel morphogenesis of vocal and auditory structures. Here, we addressed this question by generating mutant mice with targeted inactivation of Dlx5/6 genes in the Sox10 lineage, which includes neural crest and otic placode derivatives that contribute to the formation of vocal tract and ear components. We show that Dlx5/6 inactivation led to simultaneous patterning defects in the outer, middle and inner ear and of the jaw, pharynx and larynx musculoskeletal systems. We further show that Dlx5/6 modulate the BMP signalling pathway in both pharyngeal arches and otic vesicle, revealing a common Dlx5/6-BMP axis acting concurrently within the Sox10 derivatives. These findings highlight a pleiotropic role of Dlx5/6 in vocal and auditory morphogenesis, thereby suggesting their contribution in the co-adaptation of effector and receptor organs and in the diversification of acoustic communication in mammals.