Neurodevelopment Organoid Modeling Service

Understanding human brain development is one of the greatest challenges in neuroscience. The intricate processes of neurogenesis, cell migration, and circuit formation are largely inaccessible to direct study, and conventional models have significant limitations. Animal models cannot fully recapitulate human-specific features, such as the unique proliferative capacity of outer radial glia (oRGs) or the massive expansion of the cortex. Similarly, 2D cell cultures lack the essential three-dimensional cytoarchitecture and complex cell-cell interactions that orchestrate development.

Creative Biolabs bridges this gap with a cutting-edge Neurodevelopmental Organoid Modeling Service. We leverage patient-derived iPSCs and CRISPR/Cas9 engineering to build high-fidelity 3D models of the developing human brain. Going beyond single organoids, we specialize in constructing functional assembloids to model the complex interplay between different brain regions, providing an unprecedented platform to investigate neurodevelopmental disorders (NDDs) with cellular and circuit-level precision.

Modeling Fundamental Processes of Human Brain Development

Our platforms are designed to deconstruct the core events of neurodevelopment, enabling mechanistic insights that were previously unattainable.

1. Progenitor Cell Dynamics & Neurogenesis: We generate organoids that recapitulate the layered organization of the cortical plate, complete with ventricular zone-like structures containing proliferating neural progenitors. This allows for the precise study of progenitor proliferation, cell cycle kinetics, and the switch from symmetric to asymmetric division—processes frequently disrupted in disorders like microcephaly and macrocephaly.
2. Neuronal Migration and Cortical Assembly: The proper positioning of neurons is critical for circuit formation. By fusing dorsal (cortical) and ventral (MGE-like) forebrain organoids, we create forebrain assembloids that model the saltatory migration of GABAergic interneurons into the cortex. This platform is invaluable for studying cortical malformations and disorders of excitatory-inhibitory balance, like epilepsy and autism.
3. Axonal Pathfinding and Long-Range Connectivity: We model the formation of major neural tracts by generating assembloids of distinct brain regions. Thalamocortical assembloids allow for the analysis of reciprocal axonal projections between the thalamus and cortex, while cortico-striatal assembloids are used to study circuits relevant to Huntington's disease and certain NDDs.
4. Neuro-Glial and Immune Interactions: We generate complex, multi-lineage organoids by incorporating iPSC-derived microglia and astrocytes. This is essential for studying the role of neuroinflammation, synaptic pruning by microglia, and astrocyte-mediated neuronal support during development.

Applications in Modeling Neurodevelopmental Disorders

Our organoid and assembloid platforms provide robust models for a wide range of NDDs, allowing for the investigation of disease-specific cellular phenotypes.

1. Autism Spectrum Disorders (ASD) & Syndromic NDDs: We model monogenic forms of autism to study underlying mechanisms. For instance, models of Fragile X Syndrome (FMR1) can be used to investigate defects in progenitor proliferation and neuronal differentiation. Models of Rett Syndrome (MECP2) recapitulate deficits in neurogenesis and synaptic function, while Timothy Syndrome (CACNA1C) assembloids reveal cell-autonomous defects in interneuron migration.
2. Cortical Malformations (Microcephaly & Lissencephaly): We generate patient-derived or CRISPR-engineered organoids to model these conditions. Models of primary microcephaly (e.g., CDK5RAP2, WDR62 mutations) successfully show reduced organoid size and premature neurogenesis. We can also model the impact of environmental factors, such as the teratogenic effects of the Zika virus, which causes microcephaly by targeting and depleting neural progenitor cells.
3. Epilepsy and Channelopathies: By leveraging functional readouts like multi-electrode arrays (MEAs), we can study network hyperexcitability. Patient-derived organoids for conditions like Angelman Syndrome (UBE3A) show spontaneous burst firing and increased network synchronization that can be pharmacologically rescued.

Our Workflow

Deconstruct the Complexity of Neurodevelopment. Build the Foundation for New Therapies.

Leverage the power of human-specific organoid and assembloid models to accelerate your research.

Discuss Your Project with a Scientist

Reference

1. Dionne, Olivier et al. "Deciphering the physiopathology of neurodevelopmental disorders using brain organoids." Brain: a journal of neurology vol. 148,1 (2025): 12-26. doi:10.1093/brain/awae281. Distributed under Open Access License CC BY 4.0 without modification.