Abstract: Neocortical organoids derived from human pluripotent stem cells (hPSCs) have emerged as an accessible and invaluable tool to study human neurodevelopment and disease. Neocortical organoids consistently self-organize into the laminar architecture of the human cortex dorsoventrally. However, neocortical organoids currently still lack a controlled induction in the anteroposterior axis. Here, we demonstrate the polarization of neocortical organoids with the activation of anteroposterior signaling activations. We observed organizer formations that in turn self-polarize into distinct areal signatures. Many neurodevelopmental disorders have specific dysregulation in different areas within the neocortex. Thus, the demonstration of the anteroposterior polarization would serve as a powerful platform to study various neurological disorders that have differential effects on neocortical areas.
Funding Source: This work was supported by the NIH R00HD096105, NSF RECODE 2225624, New Investigator Faculty Award and startup funds to MW, the FRAXA Postdoctoral Fellowship to YCT, the CIRM Postdoctoral Fellowship (EDUC-12822) to HO.
