The temporal balance between self-renewal and differentiation of human neural stem cells requires the Amyloid Precursor Protein

• DOI: 10.1101/2021.02.17.431707
• Publication Date: 2021-02-18T04:45:17Z
• Authors: Khadijeh Shabani; Julien Pigeon; Marwan Benaissa T...; Tengyuan Liu; Azadeh Saffarian; Jun Komatsu; Elise Liu; Natasha Danda; Ridha Limame; Delphine Bohl; Carlos Parras; Bassem A. Hassan
• Keywords: Progenitor; Neocortex

Abstract The approximately 16 billion neurons of the human neocortex are derived from a relatively limited number developmental neural stem cells (NSCs). During embryogenesis, cortical NSCs initially generate at particularly slow rate while preserving their progenitor state for long time. How this balance between and neurogenic is regulated, whether it contributes to species-specific brain patterning, poorly understood. Here we show that characteristic potential remain in as they prolonged amount time requires Amyloid Precursor Protein (APP). In contrast, APP dispensable mouse NSCs, which undergo neurogenesis much faster rate. Mechanistically, loss cell-autonomously accelerates through activation AP1 transcription factor repression WNT signaling. We propose fine self-renewal differentiation homeostatically regulated by APP, may contribute human-specific temporal patterns neurogenesis.