biostudies-literatureFranks NEGeorge M. O'Brien Michigan Kidney Translational Core CenterNCI NIH HHSNational Institutes of HealthGeorge M. O'Brien Michigan Kidney Translational Core CenterNIH HHSdev203012https://www.ebi.ac.uk/biostudies/studies/S-EPMC11795293biostudies-literatureUnknown151(24)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 throughDevelopment (Cambridge, England)Hedgehog-dependent and hedgehog-independent roles for growth arrest specific 1 in mammalian kidney morphogenesis.PMC11795293R01 CA275182Franks NEAllen BLfalseHedgehog-dependent and hedgehog-independent roles for growth arrest specific 1 in mammalian kidney morphogenesis.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 through2024-01-01T00:00:00Z2024 Dec2026-06-07T05:08:10.487Z2026-06-07T03:07:13.222ZS-EPMC117952933962952210.1242/dev.203012