Project Details
Projekt
Sex-specific dynamics of epigenetic gene regulation in the developing brain
Subject Area
Developmental Neurobiology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 563470385
The formation of the mammalian brain is characterized by high cell type diversity and begins in the early stages of prenatal development through a series of crucial processes that produce the cells, form distinct anatomical regions, and fine-tune the intricate network of neural connections throughout the central nervous system. An equally intriguing aspect of neural development that is not well understood is the establishment of sex-specific characteristics that tailor physiological processes and certain behavioral patterns to be distinct between males and females. These distinctions also play a crucial role in influencing susceptibility to various conditions such as neurodevelopmental, neurodegenrative, and psychiatric disorders. Despite advancements in brain imaging and transcriptome analysis that revealed sex dimorphism across brain regions and cell types, our understanding of these distinctions at the individual cell level, especially during development, remains incomplete. Furthermore, we still lack a thorough understanding of the underlying causes of sex-specific gene expression patterns and the influence of epigenetic mechanisms at chromatin level. Hence, we here propose a comprehensive dual strategy to address open questions on the intricate interactions between (epi)genetic and hormonal regulation. We will combine an i) experimental approach leveraging our expertise in mouse models and employing advanced single-cell multiome profiling of the transcriptome and epigenome with ii) computational approaches for identifying epigenome-transciptome linkages and gene-regulatory networks. By merging these complementary areas of expertise, we seek to gain deeper insights into how sex-dependent hormone level during development provide key signals to gene expression and the underlying chromatin (accessibility) in single cells. Our project aims to decipher the adaptation of the epigenome to hormonal cues during development and unravel the sex-dimorphic consequences such as masculinization versus non-masculinization of the brain in males and females at the nexus of genetics and hormones. Using organotypic brain slices, we then investigate the underlying mechanisms of the identified transcription factors and epigenetic regulators. Finally, we will ensure that the computational methods developed in our project are accessible as user-friendly software tools and platforms for data exploration. This approach will promote sharing of both methods and data within EPIADAPT and extend to the wider research community.
DFG Programme
Priority Programmes
