Related Experiment Video
Updated: Jan 24, 2026

Feeder-free Derivation of Neural Crest Progenitor Cells from Human Pluripotent Stem Cells
Published on: May 22, 2014
Neural crest cell-derived DKK1 and NEDD4 modulate Wnt signalling in the second heart field to orchestrate outflow
Sophie Wiszniak1,2, Dimuthu Alankarage3,4, Iman Lohraseb5
1Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia. Sophie.wiszniak@adelaide.edu.au.
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 role for neural crest cells as a rheostat of Wnt signalling in cardiac progenitors, identifying a new molecular pathway promoting outflow tract morphogenesis, and a new causative factor of congenital heart disease.
Related Concept Videos
Canonical Wnt Signaling Pathway
Non-Canonical Wnt Signaling Pathways
Development of the Heart
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart...
What is Cell Signaling?
Cell-surface Signaling
Cell Signaling in Plants

