Comprehensive mapping of Neurofibromin (NF1) expression in developing mouse brain

Neurofibromin (NF1) is a critical negative regulator of the RAS-RAF-ERK pathway, mutations in which have been clinically implicated in various neurodevelopmental disorders. However, the lack of a high-resolution spatiotemporal map has obscured the understanding of why specific cell populations and developmental processes are uniquely vulnerable to NF1 loss. In this study, we present a comprehensive atlas of NF1 expression in the developing mouse brain. Using in situ hybridization and immunohistochemistry, we characterized the spatial distribution of NF1 expression from early embryonic stages through postnatal maturation. We further integrated these findings with reanalysis of single-nuclei RNA-sequencing (snRNA-seq) datasets from adult mouse brain to achieve higher resolution. Our results reveal a previously undocumented graded expression pattern of NF1 across various brain regions and cell lineages. This comprehensive study will not only help us understand the fundamental role of NF1 in brain development but will also be pivotal in providing a framework for studying NF1-associated brain disorders.