Foxp1 expression is essential for sex-specific murine neonatal ultrasonic vocalization
| Autor: | Henning Fröhlich, Rafiullah Rafiullah, Nathalie Schmitt, Gudrun A. Rappold, Sonja Abele |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Apraxias Embryonic Development Striatum Biology Medium spiny neuron Mice 03 medical and health sciences 0302 clinical medicine Intellectual Disability Internal medicine Cortex (anatomy) Genetics medicine Animals Humans Autistic Disorder Molecular Biology Genetics (clinical) Mice Knockout Regulation of gene expression Sex Characteristics Sexual differentiation Gene Expression Regulation Developmental Forkhead Transcription Factors FOXP2 General Medicine Anatomy Corpus Striatum Repressor Proteins Androgen receptor Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Ultrasonic Waves Receptors Androgen Vocalization Animal 030217 neurology & neurosurgery Sex characteristics |
| Zdroj: | Human Molecular Genetics. 26:1511-1521 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Autism and speech and language deficits are predominantly found in boys, however the causative mechanisms for this sex bias are unknown. Human FOXP1 is associated with autism, intellectual disability and speech and language deficits. Its closely related family member FOXP2 is involved in speech and language disorder and Foxp2 deficient mice have demonstrated an absence of ultrasonic vocalizations (USVs). Since Foxp1 and Foxp2 form heterodimers for transcriptional regulation, we investigated USV in neonatal brain-specific Foxp1 KO mice. Foxp1 KO pups had strongly reduced USV and lacked the sex-specific call rate from WT pups, indicating that Foxp1 is essential for normal USV. As expression differences of Foxp1 or Foxp2 could explain the sex-dimorphic vocalization in WT animals, we quantified both proteins in the striatum and cortex at P7.5 and detected a sex-specific expression of Foxp2 in the striatum. We further analyzed Foxp1 and Foxp2 expression in the striatum and cortex of CD1 mice at different embryonic and postnatal stages and observed sex differences in both genes at E17.5 and P7.5. Sex hormones, especially androgens are known to play a crucial role in the sexual differentiation of vocalizations in many vertebrates. We show that Foxp1 and the androgen receptor are co-expressed in striatal medium spiny neurons and that brain-specific androgen receptor KO (ArNesCre) mice exhibit reduced Foxp1 expression in the striatum at E17.5 and P7.5 and an increased Foxp2 level in the cortex at P7.5. Thus, androgens may contribute to sex-specific differences in Foxp1 and Foxp2 expression and USV. |
| Databáze: | OpenAIRE |
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