Molecular mechanism of breaking the anterior-posterior symmetry in a 3D synthetic human epiblast
Breaking of the anterior-posterior (a-p) symmetry at gastrulation defines the first body axis in a developing mammalian embryo. While many of the signaling pathways of this process have been elucidated in the mouse, how the initial asymmetry is established and what mechanisms drive symmetry breaking in the human remains unknown. We use human embryonic stem cells and optimize the 3D cell culture environment to reconstitute a 10-day-old human epiblast in vitro. By applying a defined dose of BMP4, one of the earliest known morphogens, our synthetic epiblast spontaneously breaks the a-p symmetry, expressing many of the molecular and morphological signatures of the primitive streak and gastrulation. We visualize symmetry breaking live using a fluorescent reporter of cell fate and by systematically knocking out the secreted inhibitors with CRISPR/Cas9, we demonstrate the key role of WNT and its inhibitor DKK1 in this process. Our synthetic epiblast opens routes to studying early developmental processes, which to date have been elusive in the human embryo.
The Rockefeller University, New York
Domain 2 - UMR 3215 / U934 - Genetics and Developmental Biology
Seminar suggested by Jean-Léon MAITRE