Core Insights - The research conducted by Tsinghua University's team addresses the "WNT signaling gradient paradox" in gastric development, which has puzzled the academic community for 20 years [1][2][3] - The study introduces a novel gastric organoid model that simulates early human gastric development, providing new pathways for organ development research and translational medicine applications [1][5] Summary by Sections WNT Signaling Gradient Paradox - The "WNT signaling gradient paradox" refers to the contradictory findings regarding the WNT signaling gradient in gastric organ development, where traditional theories suggest a gradient increase from anterior to posterior, while gastric development actually requires a decreasing gradient [2][3] - WNT proteins are crucial signaling molecules that guide embryonic development by instructing cells on tissue formation and positioning [2] Discovery of the Gastric Organoid Model - The research team proposed that the decreasing WNT signaling gradient is generated by an undiscovered "dark matter signal source," which acts as a dedicated WNT signaling regulatory center for gastric development [4] - A three-dimensional culture system was developed to accurately replicate the extracellular matrix and mechanical stimuli present during embryonic development, allowing for the successful induction of a gastric organoid model named "gastric organoid" [4][5] Mechanism of Asymmetric Gastric Development - The gastric organoid model demonstrated that the neural tissue serves as a specialized signaling center, creating a high concentration of WNT signals in the anterior region, which decreases towards the posterior, thus fulfilling the requirements for gastric development [5][6] - The study identified the epithelial transcription factor NR2F2 as a key factor in determining the asymmetric pattern of gastric tissue, revealing new mechanisms behind gastric developmental abnormalities [6][7] Theoretical and Practical Implications - The research reconstructs the signaling regulatory system of organ development, integrating neural tissue as a core regulatory component and challenging traditional single-cell lineage theories [7][8] - The gastric organoid model fills a significant gap in early human gastric development research, providing a tool for studying gastric diseases and drug development, as well as advancing the construction of artificial gastric organs [8]