Timed nucleolar shutdown restructures the developing brain genome

Helene Kretzmer, Matthew Kraushar, Michael Robson, Berlin and Potsdam

The brain is built from many different types of neurons that arise from neural progenitors during development. The neocortex, a highly evolved brain region in mammals, contains an especially diverse array of neuronal subtypes. How these subtypes are specified remains unclear, but the timed regulation of gene expression in the nucleus plays a crucial role. Our project focuses on a critical developmental window when genome activity and organization undergo rapid changes that may influence neuronal fate. We hypothesize that these large-scale changes in nuclear structure and function act as a switch, reshaping gene expression programs to guide neuron identity. To address this, our SPP2502 project will combine cutting-edge technologies to track gene expression and genome organization at single-cell resolution, and experimentally manipulate nuclear architecture and activity in the neocortex in vivo. Our interdisciplinary team brings together expertise in neurodevelopment, genome regulation, and advanced bioinformatics. Together, we aim to reveal how precisely timed nuclear dynamics control neuronal fate during neocortex development.