The role of cerebellar FOXP1 in the development of motor and communicative behaviors in mice

• Published in: Genes, brain and behavior Vol. 23; no. 5; pp. e70001 - n/a
• Main Authors: Chasse, R., McLeod, R., Surian, A., Fitch, R. H., Li, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2024; John Wiley & Sons, Inc
• Subjects: Animals; Autism; Autism Spectrum Disorder - genetics; Autism Spectrum Disorder - metabolism; Autism Spectrum Disorder - physiopathology; behavior; Cerebellum; Cerebellum - metabolism; conditional knockout; en1 cre; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; foxp1; Foxp1 protein; Foxp2 protein; genetics; Information processing; Locomotion; Male; Mesencephalon; Mice; Mice, Inbred C57BL; motor; Motor Activity - physiology; Motor skill learning; Motor task performance; mouse; Neurodevelopmental disorders; Original; Protein structure; Proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; sex differences; Social Behavior; Social discrimination learning; Spinal cord; transgenic; Vocalization behavior; Vocalization, Animal - physiology; foxp1; motor; mouse; en1 cre; genetics; transgenic; behavior; conditional knockout; cerebellum; sex differences
• ISSN: 1601-1848; 1601-183X; 1601-183X
• DOI: 10.1111/gbb.70001

The gene FOXP2 is well established for a role in human speech and language; far less is known about FOXP1. However, this related gene has also been implicated in human language development as well as disorders associated with features of autism spectrum disorder (ASD). FOXP1 protein expression has also recently been identified in the cerebellum—a neural structure previously shown to express FOXP2 protein. The current study sought to elucidate the behavioral implications of a conditional knock‐out of Foxp1 using an En1‐Cre driver, which is active in the entirety of the cerebellum and a subset of neurons in the midbrain and spinal cord, in mice using a test battery including motor tasks associated with cerebellar dysfunction, as well as communicative and autistic‐relevant behaviors. Male and female mice with a conditional knock‐out (cKO, n = 31) and wildtype littermate controls (WT, n = 34) were assessed for gross and orofacial motor control, motor‐coordination learning, locomotion, social behavior, anxiety, auditory processing and expressive vocalizations. Overall results suggest Foxp1 plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of Foxp1 in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor‐based neurodevelopmental disabilities in humans. The current study provides key insights into the role of FOXP1 in cerebellar function and associated behaviors, with implications for improved understanding of communicative and motor‐based neurodevelopmental disabilities. Overall results suggest FOXP1 may play a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex.