BAVARIAN RESEARCH ASSOCIATION INTERACTION OF HUMAN BRAIN CELLS
Identification of transcriptional networks controlling development of interhemispheric neuronal connections
Interaction of neurons in different brain regions is paramount for behavior, learning, and cognition. The corpus callosum (CC) is the largest commissural tract connecting neurons of both hemispheres of the human brain. Interhemispheric neuronal connections are central for coordination of information processing and partial as well as complete CC agenesis is considered a major contributor to cognitive impairment and associative dysfunction in intellectual disability (ID) and autism spectrum disorders.
The genetic networks underlying the formation of callosal interhemispheric connections are poorly understood. In this project, we will aim to identify transcription factor networks controlling the development of the corpus callosum. We will focus on transcription factors, whose mutations have been linked to CC agenesis in humans.
We will use ID patient-derived human induced pluripotent stem cells (hiPSC) as well as CRISPR/Cas9 genome edited human embryonic stem cells (hESCs) combined with cerebral organoid technology to model the function of these transcription factors on CC development. Next to histological and cell biological analyses, we will use single cell transcriptomics to study the impact of mutations in our genes of interest on developmental trajectories and pathways. In the second more exploratory part of this project, we aim in collaboration with TP5 (Falk/Karow) to further develop an in vitro model for CC formation, which allows to study the generation of contralateral axonal projections.
Results from this project are expected to further our understanding of the genetic networks controlling the CC development and to provide mechanistic insight into how neurodevelopmental disease genes affect the development of this enigmatic structure.
- Friedrich-Alexander-Universität Erlangen-Nürnberg