Tcf4 Controls Neuronal Migration of the Cerebral Cortex through Regulation of Bmp7.

Transcription factor 4 (TCF4) is found to be associated with schizophrenia. TCF4 mutations also cause Pitt-Hopkins Syndrome, a neurodevelopmental disorder associated with severe mental retardation. However, the function of TCF4 during brain development remains unclear. Here, we report that is expressed in the developing cerebral cortex. suppression of arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. Knockdown of impaired leading process formation. Furthermore, Bone Morphogenetic Protein 7 (Bmp7) is upregulated in -deficient neurons. gain of function and rescue experiments demonstrated that Bmp7 is the major downstream effector of required for neuronal migration. Thus, we have uncovered a new /-dependent mechanism underlying neuronal migration, and provide insights into the pathogenesis of neurodevelopmental disorders.