During neural tube (NT) development, the notochord induces an organizer, the floor plate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. In contrast, neural tube organoids (NTOs) derived from embryonic stem cells (ESCs) spontaneously form a floor plate in the absence of the notochord, demonstrating that stem cells can self-organize without embryonic inducers.
In this study, we investigated floor plate self-organization in clonal mouse NTOs. Expression of the floor plate marker FOXA2 was initially spatially dispersed before resolving into multiple clusters that underwent competition and sorting, ultimately resulting in a stable “winner” floor plate. We identified that BMP signaling governed long-range competition among clusters. FOXA2⁺ clusters expressed BMP4, which suppressed FOXA2 expression in receiving cells while simultaneously expressing the BMP inhibitor NOGGIN, thereby promoting cluster persistence.
Mutation of Noggin disrupted floor plate formation in NTOs and in vivo in the mesencephalic/rhombencephalic regions of the neural tube, demonstrating that the floor plate can autonomously form in the absence of the notochord. Identifying the pathways that govern organizer self-organization is essential for harnessing the developmental plasticity of stem cells in tissue engineering.
