The general aim of this study is to elucidate the role of the transcription factor ZFHX3 in (syndromal) intellectual disability/autism and will comprise the functional characterization of ZFHX3 during neuronal development, both in vitro and in vivo.
Hence, identifying binding partners as well as (in)direct DNA and RNA targets and their respective changes during normal neuronal differentiation, represents the starting point of the proposed research work. Subsequently, the molecular, morphological and spatial effects of ZFHX3 overexpression and knockout will be studied in vitro. In addition, zebrafish zfhx3 knockout models will be generated to study changes in neuronal networks and behavioral characteristics. Overall, this study will elucidate the role of ZFHX3 in neuronal development and provide insights why loss of function is causing disease.