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

Abstract 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 NF1 distribution from early embryonic stages through postnatal maturation. We further integrated these findings with 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 understand the fundamental role of NF1 in brain development but will also be pivotal in providing a framework for studying NF1-associated brain disorders. Summary statement Graded expression of Neurofibromin (NF1) identified across embryonic and postnatal stages reveals unique sub-lineages of neural cells in different parts of the developing mouse brain. Competing Interest Statement The authors have declared no competing interest. Footnotes The title, part of the results section, and the discussion section of the manuscript have been revised to highlight the relevance of the study in a better way. Additionally, we have added some early embryonic brain data and re-imaged some panels for better resolution. In this version, Figures 1, 2, 6, 8, and Supplementary Figure 1 have been updated.