Left-right (L-R) patterning is essential for proper organ development, and its disruption causes heterotaxy, an abnormal arrangement of internal organs, often accompanied by congenital heart defects. Although loss of the MOSMO/MEGF8/MGRN1 (MMM) complex, a membrane-tethered E3 ubiquitin ligase module, causes fully penetrant heterotaxy in mice, the underlying mechanism remains unknown. Using gastruloids, a stem-cell based model of early embryogenesis, Priscilla will investigate how the MMM complex regulates Nodal signaling, a key driver of L-R axis formation. Specifically, she will study whether the MMM complex controls the abundance of the Nodal receptor ACVR2B and define how its loss alters the spatial organization of Nodal signaling during development.
