Sourcing brain abnormality

Abstract

Neurodevelopment Disruptions in the transcription factor TCF4 lie at the root of Pitt-Hopkins syndrome (PTHS), which manifests with intellectual disability and disruptions in brain development. Schoof et al. generated mice with inducible and tissue-specific truncation of TCF4 to ensure that gene disruption occurs only in the central nervous system. The truncated protein lacks the DNA-binding domain of TCF4, a mutational hotspot for PTHS. Embryonic mice with this truncated TCF4 showed deficits in differentiation and migration of neural precursor cells. During postnatal development, Cajal-Retzius cells were misplaced and hippocampal development was disrupted. The corpus callosum, which is the fiber tract connecting the brain hemispheres, also developed poorly in these mice. These findings thus map the anatomical abnormalities that underlie this syndrome. Eur. J. Neurosci. 10.1111/ejn.14674 (2020).