A5058185294- Axon Guidance and Neuronal Signaling
- Hereditary Neurological Disorders
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Nerve injury and regeneration
- Neurological diseases and metabolism
- Cellular Mechanics and Interactions
- Ubiquitin and proteasome pathways
- Angiogenesis and VEGF in Cancer
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Retinal Development and Disorders
- Signaling Pathways in Disease
- Genetics and Neurodevelopmental Disorders
- Bioactive Compounds and Antitumor Agents
- Nuclear Structure and Function
- Autism Spectrum Disorder Research
- RNA Research and Splicing
- Zebrafish Biomedical Research Applications
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Botulinum Toxin and Related Neurological Disorders
Institut de la Vision
2021-2025
Inserm
2013-2025
Centre National de la Recherche Scientifique
2010-2025
Sorbonne Université
2012-2025
Neurosciences Paris-Seine
2015-2024
Institut de Biologie Paris-Seine
2018-2024
Université Paris-Saclay
2006-2007
Université d'Évry Val-d'Essonne
2004-2006
Mutations of the spastin gene (Sp) are responsible for most frequent autosomal dominant form spastic paraplegia, a disease characterized by degeneration corticospinal tracts. We show that deletion in mouse Sp gene, generating premature stop codon, is progressive axonal degeneration, restricted to central nervous system, leading late and mild motor defect. The degenerative process focal swellings, associated with abnormal accumulation organelles cytoskeletal components. In culture, mutant...
Mechanisms coordinating endosomal degradation and recycling are poorly understood, as the cellular roles of microtubule (MT) severing. We show that cells lacking MT-severing protein spastin had increased tubulation defective receptor sorting through tubular compartments. Spastin required ability to sever MTs interact with ESCRT-III (a complex controlling cargo degradation) proteins regulate tubulation. Cells IST1 (increased sodium tolerance 1), an for transport (ESCRT) component which binds,...
Summary Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for most frequent form of hereditary spastic paraplegia (HSP), a heterogeneous group genetic diseases characterized by degeneration corticospinal tracts. We previously reported that mice harboring deletion Spg4, generating premature stop codon, develop progressive axonal focal swellings associated with impaired transport. To further characterize molecular and cellular mechanisms underlying this...
The axon initial segment (AIS) is required for generating action potentials and maintaining neuronal polarity. Significant progress has been made in deciphering the basic building blocks composing AIS, but underlying mechanisms AIS formation remains unclear. scaffolding protein ankyrin-G master-organizer of AIS. Microtubules their interactors, particularly end-binding proteins (EBs), have emerged as potential key players formation. Here, we show that longest isoform (480AnkG) selectively...
Signal transduction downstream of axon guidance molecules is essential to steer developing axons. Second messengers including cAMP are key shared by a multitude signaling pathways and required for wide range cellular processes pathfinding. Yet, how these achieve specificity each their remains elusive. Subcellular compartmentation emerged as flexible strategy reach such specificity. Here, we show that point contact-restricted signals control ephrin-A5-evoked repulsion in vitro modulating...
During neural circuit assembly, extrinsic signals are integrated into changes in growth cone (GC) cytoskeleton underlying axon guidance decisions. Microtubules (MTs) were shown to play an instructive role GC steering. However, the numerous actors required for MT remodeling during navigation and their precise mode of action far from being deciphered. Using loss- gain-of-function analyses zebrafish development, we identify this study meiotic clade adenosine triphosphatase Fidgetin-like 1...
Functional analyses of genes responsible for neurodegenerative disorders have unveiled crucial links between processes and key developmental signalling pathways. Mutations in SPG4-encoding spastin cause hereditary spastic paraplegia (HSP). Spastin is involved diverse cellular that couple microtubule severing to membrane remodelling. Two main isoforms are synthesised from alternative translational start sites (M1 M87). However, their specific roles neuronal development homeostasis remain...
Neuronal connectivity relies on molecular motor-based axonal transport of diverse cargoes. Yet the precise players and regulatory mechanisms orchestrating such trafficking events remain largely unknown. We here report ATPase Fignl1 as a novel regulator bidirectional during axon navigation. Using yeast two-hybrid screen coimmunoprecipitation assays, we showed that binds kinesin Kif1bβ dynein/dynactin adaptor Bicaudal D-1 (Bicd1) in complex including dynactin subunit 1. colocalized with...
In most mammals, retinal ganglion cell axons from each retina project to both sides of the brain. The segregation ipsi and contralateral projections into eye-specific territories in their main brain targets—the dorsolateral geniculate nucleus superior colliculus—is critical for processing visual information. investigation developmental mechanisms contributing wiring this binocular map mammals identified competitive between while interactions same eye were challenging explore. Studies...
Abstract The microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling this network by selective activation microtubule-regulating proteins, including severers, emerged as central process in wiring. Tubulin posttranslational modifications control both properties and the activities their interacting proteins. However, whether how tubulin may contribute to connectivity has not yet been addressed. During zebrafish embryogenesis, we show that...
Abstract Signal transduction downstream of axon guidance molecules is essential to steer developing axons. Second messengers including cAMP are key shared by a multitude signaling pathways and required for wide range cellular processes pathfinding. Yet, how these achieve specificity each their remains elusive. Subcellular compartmentation emerged as flexible strategy reach such specificity. Here, we show that point contact-restricted signals control ephrin-A5-evoked repulsion in vitro...
> Les neuropathies peripheriques hereditaires, dont la prevalence est d’environ 1/5000, sont les maladies monogeniques du systeme nerveux plus frequentes. Ce grand groupe de maladies, tres heterogene tant sur le plan clinique que genetique, presente une caracteristique commune, l’atteinte progressive des nerfs peripheriques. L’analyse vitesses conduction nerveuse a l’aide l’examen electromyographique permet distinguer deux grands types neuropathies, formes demyelinisantes incluant maladie...