2026-08-20 カリフォルニア大学アーバイン校（UCI）
＜関連情報＞
- https://news.uci.edu/2026/08/20/lab-grown-brain-models-gain-a-sense-of-place/
- https://www.sciencedirect.com/science/article/pii/S1934590926002742
形態形成因子誘導による前後方向の領域同一性を有する新皮質オルガノイド Morphogen-guided neocortical organoids with anteroposterior areal identity
Yuan-Chen Tsai, Hajime Ozaki, Axel A. Almet, Isabel Fleming, Caihao Nie, Songhao Luo, Xinyi Wang, Kaori Shiraiwa, Matthew Jung Min Noh, Sunnyana Trejo, Bret Kiyoshi Sugita, Jiya Dalal, Ruben Alberto Gonzalez, Briana De Jesus, Nate Branco, Gregory Li-Min Chen, Michael J. Gandal, Qing Nie, Momoko Watanabe
Cell Stem Cell Available online: 20 August 2026
DOI:https://doi.org/10.1016/j.stem.2026.07.014
Highlights
- A simple method to make neocortical organoids with anterior-posterior signatures
- Short exposure to morphogens induced anterior and posterior organizer formation
- Area-specific signatures of polarized neocortical organoids match prenatal cortex
- Polarized organoids model area-specific phenotypes in neurodevelopmental disorders
Summary
The human neocortex exhibits characteristic regional patterning (arealization) critical for higher-order cognitive function. Disrupted arealization is implicated in neurodevelopmental disorders (NDDs), but current neocortical organoid models largely fail to recapitulate this patterning, limiting mechanistic understanding. We establish a straightforward method for generating arealized organoids through short-term early exposure to anterior or posterior morphogens. These treatments created distinct anteroposterior (AP) signaling centers, supporting long-lasting polarization validated by spatial and single-cell RNA sequencing, which revealed area-specific molecular signatures matching the prenatal human cortex. To demonstrate utility, we modeled fragile X syndrome (FXS) in organoids with distinct AP identities. FXS organoids showed disrupted expression gradients along the AP axis, consistent with alterations in autism spectrum disorder, demonstrating how regional patterning defects may contribute to NDD pathology. Together, our study provides a robust platform for generating neocortical organoids with AP molecular signatures and highlights the importance of modeling NDDs using experimental platforms with neuroanatomic specificity.
