| First Author | Franks NE | Year | 2024 |
| Journal | Development | Volume | 151 |
| Issue | 24 | PubMed ID | 39629522 |
| Mgi Jnum | J:361259 | Mgi Id | MGI:7856450 |
| Doi | 10.1242/dev.203012 | Citation | Franks NE, et al. (2024) Hedgehog-dependent and hedgehog-independent roles for growth arrest specific 1 in mammalian kidney morphogenesis. Development 151(24):dev203012 |
| abstractText | 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. |
