Rett syndrome is a severe neurodevelopmental disorder. In more than 90% of the patients, MECP2 alterations are present. However, in atypical Rett Syndrome, a MECP2 alteration can only be found in 50-70% of the cases. Alterations in MEF2C and FOXG1 have also been implicated in typical and atypical Rett Syndrome. Both genes present with a specific spatiotemporal expression pattern. This strict regulation suggests an important role for regulatory sequences at these loci. Interestingly, several deletions as well as translocations 5’ to MEF2C have been reported in patients with Rett-like manifestations. The same holds true for FOXG1, where a number of deletions 3’ to FOXG1 have been described in patients with (a)typical Rett Syndrome. As these aberrations solely affect noncoding regions, this is indicative of deletion/translocation of a crucial regulatory element. The aim of this project is to identify such regulatory elements and functionally validate the impact of element disruption. To do this, we will dissect the regulatory landscape of MEF2C and FOXG1 in the wildtype situation (1) and (2) after disruption of specific regulatory elements, (3) assess the in vivo activity pattern of these regulatory sequences and (4) determine whether the regions resulting from (1) & (2) are transcribed as enhancer RNAs (eRNAs). This will give us valuable information on the regulation of these genes and the pathways involved and might even open up possibilities for therapeutic targets