The Onecut transcriptional activators regulate multiple aspects of neuronal differentiation in the tencephalon and in the spinal cord. In addition, they are transiently detected in sensory neurons during their initial phases of development. The goal of the project is to characterize the roles that Onecuts play in sensory neuron development and to identify their mechanisms of action. We observed that Onecut factors regulate several aspects of the early stages of sensory differentiation. Mutant embryos are analyzed using light-sheet microscopy to characterize the size of dorsal root ganglion (DRG) and of each sensory neuron population, differentiation of each sensory neuron subtype and projections of these sensory neurons.
The purpose of our project is to investigate the effect of three dietary interventions containing galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS) or the combination of both in autism spectrum disorders (ASD) treatment using a valproic acid (VPA) model for ASD. In order to assess the effects of the dietary interventions in ASD progression, we are using light sheet microscopy to investigate the number and the location of the serotonergic cells in dorsal raphe nuclei of the different experimental groups.
The hexanucleotide repeat expansion in C9ORF72 is the major identified cause of ALS. Brain imaging studies show that ALS patients have significantly reduced cortical thickness when compared to other motor diseases and healthy controls. We are establishing a cortical 3D organoid model to study cortical thinning in vitro. Such a model will be a valuable tool to assess when and where neuronal death occurs in the brain and also to study the role of glial cells. For a comprehensive analysis of the organoids, we are establishing tissue clearing and whole organoid imaging protocols.
We study the molecular mechanisms that regulate brain development. We want to understand how neuronal connections are established and study the involvement and function of a family of axon guidance molecules called Semaphorins and their receptors Plexins. At the MIND facility we use lightsheet fluorescence microscopy (LSFM) to visualize embryonic and postnatal whole brain samples at cellular resolution. Using different staining and clearing methods, we can study the intact brain and reconstruct its architecture in 3D (using Imaris and ClearMap). Clearing techniques and image analysis software are changing rapidly providing endless possibilities to study the brain during development and in adulthood.
The habenula is a diencephalic midbrain structure that relays information between the forebrain and several mid- and hindbrain regions. It plays an important role in negative reward prediction and is linked to depression. Exactly when and how habenula neurons are born and form connections is not well described. Using 3DISCO clearing and staining method in combination with light sheet microscopy we visualize the developing mouse habenula. This enables us to qualitatively and quantitatively assess the habenula and its connections to the midbrain dopamine system.
The cerebellum is organized into modules identified based on anatomical connectivity and gene expression. Despite decades of studies, there is no general concept to understand the functional consequences of the anatomical, molecular and physiological differences existing between modules. Through the use of single axon reconstruction of Rabies-traced neurons, we investigate the inter- and intra-module connectivity. iDISCO clearing and light sheet microscopy are the keystone of this approach to refine the anatomy of cerebellar modules network. With this work, we aim to reveal how this assembly of modules ensure proper cerebellar information processing for optimal coordination of timing and force during movement.
We study an important genetic risk factor in Alzheimer’s Disease: ApoE isoform 4. ApoE is mainly expressed in astrocytes, a major glial cell type which, among other functions, has a neurotropic function in the normal brain. We are investigating how the ApoE genotype affects the interaction between astrocytes and neurons at the level of the synapse. For this we use iPSC-derived astrocytes and neurons and cerebral organoids to study the interaction between different cell types in a human model. Genome-editing strategies are used to insert marker genes in relevant genomic loci for labelling specific cellular subsets and for repairing genetic defects.