cerebral organoids

Cellular crosstalk in Neurodevelopmental Disorders

Cellular crosstalk is an essential process during brain development and it is influenced by numerous factors, including the morphology of the cells, their adhesion molecules, the local extracellular matrix and the secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the correct development of the human brain. Hence, we combine the in vivo mouse model and the in vitro human-derived neurons, cerebral organoids, and dorso-ventral assembloids in order to better comprehend the molecular and cellular mechanisms involved in ventral progenitors’ proliferation and fate as well as migration and maturation of inhibitory neurons during human brain development and tackle the causes of neurodevelopmental disorders. We particularly focus on mutations in genes influencing cell-cell contacts, extracellular matrix, and secretion of vesicles and therefore study intrinsic and extrinsic mechanisms contributing to the formation of the brain. Our data reveal an important contribution of cell non-autonomous mechanisms in the development of neurodevelopmental disorders.

Exploring mechanisms of human brain expansion in cerebral organoids

The human brain sets us apart as a species, with its size being one of its most striking features. Brain size is largely determined during development as vast numbers of neurons and supportive glia are generated. In an effort to better understand the events that determine the human brain’s cellular makeup, and its size, we use a human model system in a dish, called cerebral organoids. These 3D tissues are generated from pluripotent stem cells through neural differentiation and a supportive 3D microenvironment to generate organoids with the same tissue architecture as the early human fetal brain. Such organoids are allowing us to tackle questions previously impossible with more traditional approaches. Indeed, our recent findings provide insight into regulation of brain size and neuron number across ape species, identifying key stages of early neural stem cell expansion that set up a larger starting cell number to enable the production of increased numbers of neurons. We are also investigating the role of extrinsic regulators in determining numbers and types of neurons produced in the human cerebral cortex. Overall, our findings are pointing to key, human-specific aspects of brain development and function, that have important implications for neurological disease.

Modeling human development and disease in cerebral organoids

Multiplexing and Demultiplexing with cerebral organoids for neurological diseases

Genetic screening and modeling of human-specific neurogenesis in cerebral organoids

Computational tool for comparing development of cellular-scale network activity from microelectrode array (MEA) recordings of 2D neuronal cultures and 3D human cerebral organoids

CETN3 deficiency perturbs proliferation and differentiation of neural stem cells in the developing human cerebral organoids

FENS Forum 2024

Identification of changes in the electrophysiological activities in mature human cerebral organoids

Modelling Koolen-de Vries Syndrome in Cerebral Organoids

Hippocampal cerebral organoids as novel tool for regenerative medicine

FENS Forum 2024

Interrogating CDKL5 deficiency disorder using human iPSCs-derived cerebral organoids

FENS Forum 2024

Mutant huntingtin disrupts global DNA methylation in human iPSC-derived cerebral organoids

FENS Forum 2024

LPS and pre-aggregated Abeta 1-42 lead to an increased neuroinflammatory response in cerebral organoids

FENS Forum 2024

The role of the ASD-associated 16p11.2 gene QPRT during differentiation of human embryonic stem cell-derived cerebral organoids

FENS Forum 2024

Single-cell CRISPR screening in cerebral organoids identifies developmental and cell type-specific defects of autism

FENS Forum 2024