Journal of Psychiatry

Gender-dimorphic expression of Foxp1 in the developing mouse brain and its impact on sex-specific communication

2^nd International Conference on Psychiatry and Psychiatric Disorders

May 02-04, 2016 Chicago, Illinois, USA

Gudrun A Rappold, Henning Frohlich, Rafiullah Rafiullah, Sonja Abele and Claire Bacon

University of Heidelberg, Germany

Posters & Accepted Abstracts: J Psychiatry

Abstract:

Autism spectrum disorder (ASD) as well as speech and language deficits are four times more prevalent in males than females. The reason for this is still unknown, although it has been suggested that sex-specific regulation of distinct genes may promote the development of ASD. The human Foxp1 gene represents an interesting candidate as Foxp1 mutations have been associated with intellectual disability, speech and language deficits and ASD in predominantly male patients. The Foxp1 gene belongs to the family of fork head box (FOX) transcription factors and is widely expressed in the developing and mature brain. Homozygous loss of Foxp1 is embryonically lethal in mouse due to cardiac defects. To investigate the role of Foxp1 in neuro-developmental processes, we generated Nestin-Cre (Foxp1-/-) mice with conditional loss of Foxp1 in the brain. We could demonstrate that Foxp1 is crucial for the development of the striatum and hippocampus but also for normal learning, memory and social behaviors. We also observed that male Foxp1-KO animals exhibit a more severe phenotype and die earlier than female Foxp1-KO mice. To investigate whether this sexual dimorphic phenotype of Foxp1-KO animals is caused by gender-specific expression and function of Foxp1, we explored the differences in the expression of Foxp1 in male and female WT animals at six different stages of brain development in the cortex, striatum, hippocampus and cerebellum. We also examined the expression level of Foxp2, the closest relative of Foxp1, which is associated with language disorder. Foxp2 is known to form hetero-dimers in those tissues where it is co-expressed with Foxp1, such as the striatum. Our study revealed sexually dimorphic expression of Foxp1 and Foxp2 in the striatum and cortex at E 17.5 and P 7.5. Both the cortex and striatum are known to be crucial for language and communication. Interestingly, at about E 17.5 testosterone levels peak in male embryos suggesting that the observed sex-dimorphic expression may be caused by a gender-specific androgen or estrogen signaling.

Biography :

Email: gudrun_rappold@med.uni-heidelberg.de