Neural crest cell-derived DKK1 and NEDD4 modulate Wnt signalling in the second heart field to orchestrate outflow tract development.

ABSTRACT: Cardiac outflow tract morphogenesis requires coordinated interactions between multiple cell populations and is dependent on the contribution of cardiac progenitors from the second heart field. While neural crest cells have been proposed to impact second heart field development, how they regulate progenitor behaviour remains unclear. Here, we discover neural crest cells are a primary source of Dickkopf-1 (DKK1) which modulates Wnt signalling activity in the second heart field to influence the balance between cardiac progenitor maintenance and differentiation. We show that the ubiquitin ligase NEDD4 regulates DKK1, with disruption of Nedd4 leading to outflow tract defects. We further identify a new NEDD4 variant underlying human congenital heart disease. Our findings uncover an unexpected ro

SUBMITTER: Wiszniak S 

PROVIDER: S-EPMC12913648 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature