Abstract

The BMP-GREM1-SHH signaling pathways play pivotal roles in regulating cell differentiation, progenitor maintenance, and tissue development. Dysregulation of these pathways contributes to kidney malformations and cancer progression. Here, we use integrated simulations, ChIP-seq analyses, and computational models to uncover novel insights into the epigenetic regulation and feedback dynamics of BMP-GREM1-SHH pathways. Our findings reveal critical interactions in kidney morphogenesis, including SHH-BMP synergy in nephron formation and Gli3-mediated transcriptional regulation. Additionally, we identify therapeutic targets, such as GREM1 inhibitors and BMP7 mimetics, for mitigating pathway dysregulation in renal cell carcinoma (RCC). These results provide a foundation for novel therapeutic interventions and a deeper understanding of genetic regulation in development and disease.

Keywords

SHH pathway, BMP pathway, canger progression, epigenetic regulation