2024/12/04 by Nicole E. Franks, Benjamin L. Allen · 1 voice
Biochemistry, Genetics and Molecular Biology · #Epigenetics and DNA Methylation #Genetic and Kidney Cyst Diseases #Renal and related cancers
paper · doi:10.1242/dev.203012
openalex publication_date 2024/12/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Growth arrest specific 1 (GAS1) is a key regulator of mammalian embryogenesis, best known for its role in hedgehog (HH) signaling, but with additional described roles in the FGF, RET, and NOTCH pathways. Previous work indicated a later role for GAS1 in kidney development through FGF pathway modulation. Here, we demonstrate that GAS1 is essential for both mesonephrogenesis and metanephrogenesis - most notably, Gas1 deletion in mice results in renal agenesis in a genetic background-dependent fashion. Mechanistically, GAS1 promotes mesonephrogenesis in a HH-dependent fashion, performing a unique co-receptor function, while promoting metanephrogenesis in a HH-independent fashion, acting as a putative secreted RET co-receptor. Our data indicate that Gas1 deletion leads to renal agenesis through a transient reduction in metanephric mesenchyme proliferation - a phenotype that can be rescued by exogenous RET pathway stimulation. Overall, this study indicates that GAS1 contributes to early kidney development through the integration of multiple different signaling pathways.