cortical organoids

Investigating activity-dependent processes in cerebral cortex development and disease

The cerebral cortex contains an extraordinary diversity of excitatory projection neuron (PN) and inhibitory interneurons (IN), wired together to form complex circuits. Spatiotemporally coordinated execution of intrinsic molecular programs by PNs and INs and activity-dependent processes, contribute to cortical development and cortical microcircuits formation. Alterations of these delicate processes have often been associated to neurological/neurodevelopmental disorders. However, despite the groundbreaking discovery that spontaneous activity in the embryonic brain can shape regional identities of distinct cortical territories, it is still unclear whether this early activity contributes to define subtype-specific neuronal fate as well as circuit assembly. In this study, we combined in utero genetic perturbations via CRISPR/Cas9 system and pharmacological inhibition of selected ion channels with RNA-sequencing and live imaging technologies to identify the activity-regulated processes controlling the development of different cortical PN classes, their wiring and the acquisition of subtype specific features. Moreover, we generated human induced pluripotent stem cells (iPSCs) form patients affected by a severe, rare and untreatable form of developmental epileptic encephalopathy. By differentiating cortical organoids form patient-derived iPSCs we create human models of early electrical alterations for studying molecular, structural and functional consequences of the genetic mutations during cortical development. Our ultimate goal is to define the activity-conditioned processes that physiologically occur during the development of cortical circuits, to identify novel therapeutical paths to address the pathological consequences of neonatal epilepsies.

AIR-LIQUID INTERFACE CORTICAL ORGANOIDS AS A PLATFORM TO STUDY TDP-43 PATHOLOGY IN ALS

FENS Forum 2026

TBR2 COORDINATES ATP-DEPENDENT CHROMATIN REMODELING REQUIRED FOR NEURONAL DIFFERENTIATION IN HUMAN CORTICAL ORGANOIDS

FENS Forum 2026

INTEGRATION OF HUMAN IPSC- DERIVED MICROGLIA IN ADHERENT CORTICAL ORGANOIDS: STRUCTURAL AND FUNCTIONAL INSIGHTS

FENS Forum 2026

MYELIN-DERIVED FATTY ACIDS AMELIORATE PATHOLOGY IN HUMAN CORTICAL ORGANOIDS FROM ALZHEIMER’S DISEASE

FENS Forum 2026

MODELING KLEEFSTRA SYNDROME USING HUMAN INDUCED PLURIPOTENT STEM CELLS (HIPSCS) DERIVED CORTICAL ORGANOIDS

FENS Forum 2026

DIMETHYL FUMARATE MITIGATES ALPHA-SYNUCLEIN–INDUCED DEFECTS IN HUMAN 3D CORTICAL ORGANOIDS AND MOUSE MODELS OF SYNUCLEOPATHY

FENS Forum 2026

PKC-NOTCH-DEPENDENT NEUROGENESIS ACTIVATION IN HUMAN CORTICAL ORGANOIDS AS A STRATEGY FOR BRAIN REPAIR

FENS Forum 2026

REPEATED INFLAMMATORY CHALLENGES INDUCE ASTROCYTE-ASSOCIATED INFLAMMATORY PRIMING AND ALZHEIMER’S DISEASE–RELATED MOLECULAR SIGNATURES IN HUMAN CORTICAL ORGANOIDS

FENS Forum 2026

VOLUME ELECTRON MICROSCOPY OF CORTICAL ORGANOIDS: METHODS FOR REGION IDENTIFICATION, CONNECTOME RECONSTRUCTION AND ORGANELLE SEGMENTATION

FENS Forum 2026

iPSC-derived cortical neurons and patterned cortical organoids to dissect the neurodevelopmental roots of Fragile X Syndrome

3D Human Cortical Organoids to investigate developmental and epileptic encephalopathy

Functional analysis of spontaneous neuronal activity in cortical organoids as a model of human tauopathies

FENS Forum 2024

Increased GABAergic neurogenesis in human cortical organoids with schizophrenia-associated SETD1A mutations

FENS Forum 2024