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In early neurodevelopment, the central nervous system is established through the coordination of various neural organizers directing tissue patterning and cell differentiation. Better recapitulation of morphogen gradient production and signaling will be crucial for establishing improved developmental models of the brain in vitro. Here, we developed a method by assembling polydimethylsiloxane devices capable of generating a sustained chemical gradient to produce patterned brain organoids, which we termed morphogen-gradient-induced brain organoids (MIBOs). At 3.5 weeks, MIBOs replicated dorsal-ventral patterning observed in the ganglionic eminences (GE). Analysis of mature MIBOs through single-cell RNA sequencing revealed distinct dorsal GE-derived CALB2 + interneurons, medium spiny neurons, and medial GE-derived cell types. Finally, we demonstrate long-term culturing capabilities with MIBOs maintaining stable neural activity in cultures grown up to 5.5 months. MIBOs demonstrate a versatile approach for generating spatially patterned brain organoids for embryonic development and disease modeling., Competing Interests: Declaration of interests The authors listed (Y.S., C.P., F.Y., and N.P. ) have filed a provisionary patent related to this work (Docket Number: UMA 23-023, Title: “A chemical gradient inducing device and methods for developing patterned organoids.”)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Research on bidirectional communication between the heart and brain has often relied on studies involving nonhuman animals. Dependance on animal models offer limited applicability to humans and a lack of high-throughput screening. Recently, the field of 3D cell biology, specifically organoid technology, has rapidly emerged as a valuable tool for studying interactions across organ systems, i.e., gut-brain axis. The initial success of organoid models indicates the usefulness of 3D cultures for elucidating the intricate interactivity of the autonomic nervous system and overall health. This perspective aims to explore the potential of advancing in vitro modeling of the heart-brain axis by discussing the benefits, applications, and adaptability of organoid technologies. We closely examine the current state of brain organoids in conjunction with the advancements of cardiac organoids. Moreover, we explore the use of combined organoid systems to investigate pathophysiology and provide a platform for treatment discovery. Finally, we address the challenges that accompany the use of 3D models for studying the heart-brain axis with an emphasis on generating tailored engineering strategies for further refinement of dynamic organ system modeling in vitro. [ABSTRACT FROM AUTHOR]