Year: 2026
Type: preprint
Abstract: Gastrulation begins when the epiblast epithelium breaks symmetry to form the primitive streak, but current in vitro models neither fully capture this process nor separate its mechanical and chemical inputs. Here, we introduce LightBMP, an optogenetic platform that enables spatiotemporally programmable BMP4 expression in human pluripotent stem cells. Dose and duration control reveal a sustained low-BMP regime, inaccessible to re-combinant ligand, that specifies mesoderm. Spatially programmed BMP4 sources in uniform cultures mimic the radial organization of 2D gastruloids, showing that mechanical context and edge sensing are not required for patterning. In micropatterned colonies, light-defined sources break symmetry to generate a stripe-shaped, primitive-streak-like domain where cells acquire multiple mesodermal fates and undergo directed migration. Together, these results show that spatial control of a single morphogen source is sufficient to drive symmetry breaking and primitive-streak-like patterning, independent of edge constraints.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Signaling Logic Underlying Mammalian Germ Layer Differentiation, Signaling dynamics in the control of ectoderm patterning and morphogenesis, Visualization of extracellular morphogens to understand self-organized patterning, Synthetic circuit technologies for precision control and signal processing in mammalian cells
OpenAlex ID: W7215905713