The phosphatase PTEN (phosphatase and tensin homologue on chromosome 10) is a key tumor suppressor gene and an important regulator of neuronal signaling. PTEN mutations have been identified in patients with autism spectrum disorders, characterized by macrocephaly, impaired social interactions and communication, repetitive behavior, intellectual disability, and epilepsy. It functions as global suppressor of growth-promoting PI3K signaling. In the first part of my talk, I will discuss mechanisms that confer spatiotemporal control of PTEN by engaging different protein-protein interactions. We identified that the transmembrane protein PRG2/LPPR3 functions as a modulator of PTEN function during axon morphogenesis. Our work demonstrates that through inhibition of PTEN, PRG2/LPPR3 controls growth capacity of extending axons, redirecting growth to axonal branches. In the second part, I will introduce our preliminary work on exploiting PTEN deficiency to understand the impact of the subplate/layer 6b as substrate for developmental disorders such as autism and epilepsy. We started examining the miswiring of the subplate induced in PTEN deficient circuits in mice as entry point for our hypothesis.
Britta Eickholt is Professor for ‘Molecular Biology and Biochemistry’ at the Charité – University Medicine Berlin. After a PhD in Biochemistry from Guy’s Hospital / King’s College London in 1998, she carried out a postdoc at the MRC Centre for Neurodevelopmental Biology in London. This is also where she started her own laboratory in 2001. The research in the Eickholt lab broadly focuses on the cellular mechanism controlling the development, maturation and maintenance of neurons and astrocytes in the brain. Her lab uses a multidisciplinary approach to understand how neurons and astrocyte establish and modify their complex shapes in the healthy brain and during disease or injury.