A5073957747- Single-cell and spatial transcriptomics
- Neural dynamics and brain function
- Neurogenesis and neuroplasticity mechanisms
- Cell Image Analysis Techniques
- Neurobiology and Insect Physiology Research
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Zebrafish Biomedical Research Applications
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Cellular transport and secretion
- Olfactory and Sensory Function Studies
- Axon Guidance and Neuronal Signaling
- Retinal Development and Disorders
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Glioma Diagnosis and Treatment
- Health, Environment, Cognitive Aging
- Nerve injury and regeneration
- Gene expression and cancer classification
- Hemispheric Asymmetry in Neuroscience
- Gene Regulatory Network Analysis
- Signaling Pathways in Disease
VIB-KU Leuven Center for Brain & Disease Research
2024
University of Geneva
2017-2024
KU Leuven
2024
Inserm
2014-2017
Sorbonne Université
2014-2017
Institut du Fer à Moulin
2014-2017
The ever-growing compendium of genetic variants associated with human pathologies demands new methods to study genotype-phenotype relationships in complex tissues a high-throughput manner1,2. Here we introduce adeno-associated virus (AAV)-mediated direct vivo single-cell CRISPR screening, termed AAV-Perturb-seq, tuneable and broadly applicable method for transcriptional linkage analysis as well high-resolution phenotyping perturbations vivo. We applied AAV-Perturb-seq using gene editing...
Cortical expansion in primate brains relies on enlargement of germinal zones during a prolonged developmental period. Although most mammals have two cortical zones, the ventricular zone (VZ) and subventricular (SVZ), gyrencephalic species display an additional zone, outer (oSVZ), which increases number diversity neurons generated corticogenesis. How oSVZ emerged evolution is poorly understood, but recent studies suggest role for non-coding RNAs, allow tight genetic program regulation...
Abstract Focal cortical dysplasia type II (FCDII) is a malformation causing refractory epilepsy. FCDII arises from developmental somatic mutations in mTOR pathway genes, leading to focal dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic how they affect cell-type-specific transcriptional programs remains unknown. To address this question, here we combined single-nucleus genotyping transcriptomics morphologically-identified cells using surgical samples...
The cerebral cortex shows species-specific variations in size and organization, likely accounting for distinct behavioral abilities. These structural differences may reflect evolutionary changes the developmental expression of shared genes. To investigate this possibility, we compared cell-type-specific gene across species developing mouse human neocortex, cortical organoids, by a transcriptional reference framework. This identified genes with conserved/divergent patterns, providing...
Abstract Neocortical excitatory neurons belong to diverse cell types, which can be distinguished by their dates of birth, laminar location, connectivity, and molecular identities. During embryogenesis, apical progenitors (APs) located in the ventricular zone first give birth deep-layer neurons, next superficial-layer neurons. While overall sequential construction neocortical layers is well-established, whether APs produce multiple neuron types at single time points corticogenesis unknown. To...
The neocortex is organized into distinct areas, whose interconnectivity underlies sensorimotor transformations and integration 1–7 . These behaviorally critical functions are mediated by intracortically-projecting neurons (ICPN), which a heterogeneous population of cells sending axonal branches to cortical areas as well subcortical targets 8–10 Although population-based 11–14 single-cell 15–19 intracortical wiring diagrams being identified, the transcriptional signatures corresponding...
ABSTRACT SCHIP1 is a cytoplasmic partner of cortical cytoskeleton ankyrins. The IQCJ-SCHIP1 isoform component axon initial segments and nodes Ranvier mature axons in peripheral central nervous systems, where it associates with membrane complexes comprising cell adhesion molecules. also expressed the mouse developing system during embryonic stages active axonogenesis. Here, we identify new early role for development establishment anterior commissure (AC). AC composed from piriform cortex,...
Abstract The axon initial segment ( AIS ) plays a central role in electrogenesis and the maintenance of neuronal polarity. Its molecular organization is dependent on scaffolding protein ankyrin (Ank) G regulated by kinases. For example, phosphorylation voltage‐gated sodium channels kinase CK 2 regulates their interaction with AnkG and, consequently, accumulation at . We previously showed that IQ motif containing J‐Schwannomin‐Interacting Protein 1 IQCJ ‐ SCHIP ‐1), an isoform ‐1, accumulated...
Brains come in various sizes and shapes, yet how neuronal position constrains the type of circuits that they can form remains largely unknown. The spatial layout anatomical structures with corresponding functions varies widely across species. Also, during evolution, have duplicated then diverged to generate new functions. Thus, it is critical understand neurons their integration into and, ultimately, function. To address this question, we studied Eml1 knockout mice which subsets neocortical...
Cellular diversity in the neocortex emerges gradually during prenatal and postnatal development. While environmental interactions occur this extended maturation period, impact of extrinsic cues on determining fate distinct neuron types remains unknown. To address question, we exposed developing neocortical cells to various conditions examined how affects cell diversity. Our developmental analyses reveal a hierarchical molecular program which class-distinguishing features emerge first,...
Abstract Distinct subtypes of intracortically-projecting neurons (ICPN) are present in all layers, allowing propagation information within and across cortical columns. How the molecular identities ICPN relate to their defining anatomical functional properties is unknown. Here we show that transcriptional primarily reflect input-output connectivities rather than birth dates or laminar positions. Thus, conserved circuit-related programs at play which may preserve canonical circuit features...
Cortical expansion in the primate brain relies on presence and spatial enlargement of multiple germinal zones during development a prolonged developmental period. In contrast to other mammals, which have two cortical zones, ventricular zone (VZ) subventricular (SVZ), gyrencephalic species display an additional zone, outer (OSVZ), role is increase number types neurons generated corticogenesis. How OSVZ emerged evolution poorly understood but recent studies suggest for non-coding RNAs, allow...