Fadel Tissir

Fadel Tissir
Université Catholique de Louvain - UCLouvain | UCLouvain · Institute of Neuroscience

PhD

About

138
Publications
18,490
Reads
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4,805
Citations
Citations since 2017
43 Research Items
2104 Citations
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20172018201920202021202220230100200300400
20172018201920202021202220230100200300400
20172018201920202021202220230100200300400
Additional affiliations
September 2001 - June 2017
Université Catholique de Louvain - UCLouvain
Position
  • Managing Director
September 2001 - June 2017
Université Catholique de Louvain - UCLouvain
Position
  • Managing Director

Publications

Publications (138)
Article
Full-text available
Malformation of cortical development (MCD) is a family of neurodevelopmental disorders, which usually manifest with intellectual disability and early-life epileptic seizures. Mutations in genes encoding microtubules (MT) and MT-associated proteins are one of the most frequent causes of MCD in humans. KIF2A is an atypical kinesin that depolymerizes...
Article
KIF2A is an atypical kinesin that has the capacity to depolymerize microtubules. Patients carrying mutations in KIF2A suffer from progressive microcephaly and mental disabilities. While the role of this protein is well documented in neuronal migration, the relationship between its dysfunction and the pathobiology of brain disorders is unclear. Here...
Article
Full-text available
Neurogenesis and tumorigenesis share signaling molecules/pathways involved in cell proliferation, differentiation, migration, and death. Self- renewal of neural stem cells is a tightly regulated process that secures the accuracy of cell division and eliminates cells that undergo mitotic errors. Abnormalities in the molecular mechanisms controlling...
Article
A few developmental genes remain persistently expressed in the adult stage, whilst their potential functions in the mature brain remain underappreciated. Here, we report the unexpected importance of Celsr2, a core Planar cell polarity (PCP) component, in maintaining the structural and functional integrity of adult neocortex. Celsr2 is highly expres...
Poster
Full-text available
The conference covers topics on both developmental and adult neurogenesis.
Article
Full-text available
Understanding new modulators of axon regeneration is central to neural repair. Our previous work demonstrated critical roles of atypical cadherin Celsr2 during neural development, including cilia organization, neuron migration and axon navigation. Here, we address its role in axon regeneration. We show that Celsr2 is highly expressed in both mouse...
Article
Full-text available
Introduction: Vestibular sensory hair cells are precisely orientated according to planar cell polarity (PCP) and are key to enable mechanic-electrical transduction and normal vestibular function. PCP is found on different scales in the vestibular organs, ranging from correct hair bundle orientation, coordination of hair cell orientation with neighb...
Article
The tangential migration of immature neurons in the postnatal brain involves consecutive migration cycles and depends on constant remodeling of the cell cytoskeleton, particularly in the leading process (LP). Despite the identification of several proteins with permissive and empowering functions, the mechanisms that specify the direction of migrati...
Article
Full-text available
Atypical cadherin Celsr3 is critical for brain embryonic development, and its role in the postnatal cerebellum remains unknown. Using Celsr3-GFP mice, Celsr3 shows high expression in postnatal Purkinje cells (PCs). Mice with conditional knockout (cKO) of Celsr3 in postnatal PCs exhibit deficit in motor coordination and learning, atrophic PC dendrit...
Article
Full-text available
Neurodevelopmental disorders arise from combined defects in processes including cell proliferation, differentiation, migration and commissure formation. The evolutionarily conserved tumor-suppressor protein Scribble (Scrib) serves as a nexus to transduce signals for the establishment of apicobasal and planar cell polarity during these processes. Hu...
Article
Full-text available
Diaphanous (DIAPH) 3 is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mito...
Preprint
During development, cadherins Celsr2 and Celsr3 control axon navigation. Unlike Celsr3, Celsr2 remains expressed in the adult, suggesting unexplored roles in maintenance and repair. Here we show that Celsr2 knockdown promotes motor axon regeneration in mouse and human spinal cord explants and cultured motor neurons. Celsr2 downregulation is accompa...
Article
The molecular mechanisms by which cilia orientation is coordinated within and between multiciliated cells (MCCs) are not fully understood. In the mouse oviduct, MCCs exhibit a characteristic BB orientation and microtubule gradient along the tissue axis. The intracellular polarities were moderately maintained in the cells lacking CELSR1, a planar ce...
Article
Full-text available
Defects in protein reabsorption by the proximal tubule are toxic for epithelial cells in the nephron and may result in nephropathy. In this study, we showed that the ion channel TRPV4 modulated the endocytosis of albumin and low–molecular weight proteins in the proximal tubule. TRPV4 was found at the basolateral side of proximal tubule cells, and i...
Article
Full-text available
Paralog factors are usually described as consolidating biological systems by displaying redundant functionality in the same cells. Here, we report that paralogs can also cooperate in distinct cell populations at successive stages of differentiation. In mouse embryonic spinal cord, motor neurons and V2 interneurons differentiate from adjacent progen...
Preprint
The molecular mechanisms by which cilia orientation is coordinated within and between multiciliated cells (MCCs) is not fully understood. By observing the orientation of basal bodies (BB) in MCCs of mouse oviducts, here, we show that Celsr1, a planar cell polarity (PCP) factor involved in tissue polarity regulation, is dispensable for determining B...
Article
Full-text available
The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery¹. Although the response of epidermal cells to stretching has been studied in vitro2,3, it remains unclear how mechanical forces affect their behaviour in vivo. Here we develop a mouse model in which the consequences of stretching on skin epidermis...
Preprint
Full-text available
Diaphanous (DIAPH) 3 is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mito...
Article
Full-text available
Group I metabotropic glutamate receptors (mGluR) are involved in various forms of synaptic plasticity that are believed to underlie declarative memory. We previously showed that mGluR5 specifically activates channels containing TRPC1, an isoform of the canonical family of Transient Receptor Potential channels highly expressed in the CA1-3 regions o...
Article
Full-text available
In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present...
Preprint
Full-text available
Abstract Neurodevelopmental disorders often arise from combined defects in processes including cell proliferation, differentiation, neuronal migration, axonal pathfinding and commissure formation. Cell polarity proteins serve as a nexus to transduce signals for the establishment of these essential processes. Scribble (Scrib) is an evolutionarily co...
Article
Full-text available
Cell polarity refers to the asymmetric distribution of signaling molecules, cellular organelles, and cytoskeleton in a cell. Neural progenitors and neurons are highly polarized cells in which the cell membrane and cytoplasmic components are compartmentalized into distinct functional domains in response to internal and external cues that coordinate...
Article
Full-text available
Cajal‐Retzius neurons (CRN) are the main source of Reelin in the marginal zone of the developing neocortex and hippocampus (HC). They also express the transcription factor p73 and are complemented by later‐appearing GABAergic Reelin+ interneurons. The human dorsal HC forms at gestational week 10 (GW10), when it develops a rudimentary Ammonic plate...
Article
Full-text available
Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories...
Preprint
The proximal tubule (PT) mediates the endocytosis of essential substances filtered through the glomerulus, including albumin and a large variety of low molecular weight proteins that would otherwise be lost in urine. Variations in the amount of ultrafiltrate delivered to the PT modulate protein endocytosis. Here we show that TRPV4 ion channel is ex...
Article
Full-text available
Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct cerebrospinal fluid circulation. Thus, PCP disruption results in ciliopathies and hydrocephalus. PCP e...
Article
Full-text available
Group I metabotropic glutamate receptors, in particular mGluR5, have been implicated in various forms of synaptic plasticity that are believed to underlie declarative memory. We observed that mGluR5 specifically activated a channel containing TRPC1, an isoform of the canonical family of transient receptor potential (TRPC) channels highly expressed...
Preprint
Full-text available
Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories...
Article
Motor neurons are among the longest projection neurons and their axons extend into the periphery following highly stereotypical pathways. Motor neurons share similar guidance molecules with other projection neurons. Hence, one challenge in the field has been to understand how the vast complexity of connections can be regulated by a relatively small...
Article
Full-text available
The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this co...
Article
Cadherin EGF LAG seven-pass G-type receptors 1, 2 and 3 (CELSR1-3) form a family of three atypical cadherins with multiple functions in epithelia and in the nervous system. During the past decade, evidence has accumulated for a key role of CELSR1 in epithelial planar cell polarity (PCP), and for CELSR2 and CELSR3 in ciliogenesis and neural developm...
Article
Full-text available
Understanding the developmental steps shaping the formation of the neuromuscular junction (NMJ) connecting motoneurons to skeletal muscle fibers, is critical. Wnt morphogens are key players in the formation of this specialized peripheral synapse. Yet, the individual and collaborative functions of Wnts as well as their downstream pathways remain poo...
Article
Vestibular hair cells of the inner ear are specialized receptors that detect mechanical stimuli from gravity and motion via the deflection of a polarized bundle of stereocilia located on their apical cell surfaces. The orientation of stereociliary bundles is coordinated between neighboring cells by core PCP proteins including the large adhesive G-p...
Article
Full-text available
Cajal-Retzius cells (CRs), the first-born neurons in the developing cerebral cortex, coordinate crucial steps in the construction of functional circuits. CRs are thought to be transient, as they disappear during early postnatal life in both mice and humans, where their abnormal persistence is associated with pathological conditions. Embryonic CRs c...
Article
Full-text available
The diaphanous homologue Diaph3 (aka mDia2) is a major regulator of actin cytoskeleton. Loss of Diaph3 has been constantly associated with cytokinesis failure ascribed to impaired accumulation of actin in the cleavage furrow. Here we report that Diaph3 is required before cell fission, to ensure the accurate segregation of chromosomes. Inactivation...
Data
Supplementary Figures 1-11 and Supplementary Table 1.
Article
Peroxiredoxins are a superfamily of peroxidases widely distributed among prokaryotes and eukaryotes. Peroxiredoxin-5 (Prdx5) is the last isoform identified and characterized among the six mammalian peroxiredoxins. Prdx5 is ubiquitously expressed in tissues and its role as cytoprotective antioxidant enzyme has been largely reported in vitro. The goa...
Article
The neocortex undergoes extensive developmental growth, but how its architecture adapts to expansion remains largely unknown. Here, we investigated how early born Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits, maintain a dense superficial distribution in the growing neocortex. We found that CR cell density is sustaine...
Article
Full-text available
TRPV4 is a polymodal cation channel expressed in osmosensitive neurons of the hypothalamus and in the mammalian nephron. The segmental distribution and role(s) of TRPV4 in osmoregulation remain debated. We investigated the renal distribution pattern of TRPV4 and the functional consequences of its disruption in mouse models. Using qPCR on microdisse...
Article
The caudal migration of facial branchiomotor (FBM) neurons from rhombomere (r) 4 to r6 in the hindbrain is an excellent model to study neuronal migration mechanisms. Although several Wnt/Planar Cell Polarity (PCP) components are required for FBM neuron migration, only Celsr1, an atypical cadherin, regulates the direction of migration in mice. In Ce...
Article
A unique population of cells, called “lot cells,” circumscribes the path of the lateral olfactory tract (LOT) in the rodent brain and acts to restrict its position at the lateral margin of the telencephalon. Lot cells were believed to originate in the dorsal pallium (DP). We show that Lhx2 null mice that lack a DP show a significant increase in the...
Article
Full-text available
Sequential generation of neurons and glial cells during development is critical for the wiring and function of the cerebral cortex. This process requires accurate coordination of neural progenitor cell (NPC) fate decisions, by NPC-autonomous mechanisms as well as by negative feedback from neurons. Here, we show that neurogenesis is protracted and g...
Data
Supplementary Figures 1-10 and Supplementary Table 1
Article
Full-text available
Unlabelled: The striatum is a large brain nucleus with an important role in the control of movement and emotions. Medium spiny neurons (MSNs) are striatal output neurons forming prominent descending axon tracts that target different brain nuclei. However, how MSN axon tracts in the forebrain develop remains poorly understood. Here, we implicate th...
Article
Full-text available
In the neocortex, higher-order areas are essential to integrate sensory-motor information and have expanded in size during evolution. How higher-order areas are specified, however, remains largely unknown. Here, we show that the migration and distribution of early-born neurons, the Cajal-Retzius cells (CRs), controls the size of higher-order areas...
Article
The assembly of functional neuronal circuits depends on the correct wiring of axons and dendrites. To reach their targets, axons are guided by a variety of extracellular guidance cues, including Netrins, Ephrins, Semaphorins and Slits. Corresponding receptors in the growth cone, the dynamic structure at the tip of the growing axon, sense and integr...
Article
Full-text available
The oviduct is an important organ in reproduction where fertilization occurs, and through which the fertilized eggs are carried to the uterus in mammals. This organ is highly polarized, where the epithelium forms longitudinal folds along the ovary-uterus axis, and the epithelial multicilia beat towards the uterus to transport the ovulated ova. Here...
Article
Full-text available
The cadherin Celsr3 regulates the directional growth and targeting of axons in the CNS, but whether it acts in collaboration with or in parallel to other guidance cues is unknown. Furthermore, the function of Celsr3 in the peripheral nervous system is still largely unexplored. Here we show that Celsr3 mediates pathfinding of motor axons innervating...
Article
Full-text available
Significance Ependymal cilia are required for circulation of the cerebrospinal fluid and neurogenesis. To function properly, ependymal cilia must coordinate their beats in individual cells and across the tissue. Planar cell polarity (PCP) orients cilia in a given cell, thereby enabling their concerted beating. Here, we describe previously unidentif...
Article
Full-text available
Significance Connections are crucial to brain function and a variety of molecular systems direct axonal growth during development and regeneration. An important system involves Celsr2, Celsr3, and Fzd3, membrane proteins that also regulate epithelial planar cell polarity (PCP). Here, we show genetically that Celsr2 and Celsr3 guide axons redundantl...
Article
Full-text available
How growth cones detect small concentration differences of guidance cues for correct steering remains a long-standing puzzle. Commissural axons engage planar cell polarity (PCP) signaling components to turn anteriorly in a Wnt gradient after midline crossing. We found here that Frizzled3, a Wnt receptor, undergoes endocytosis via filopodia tips. Wn...
Data
Time-lapse movie was started 4 hr after plating of Celsr1-GFP-transfected cells. Confocal images were obtained every 10 min overnight, and seven z stack images at 1 μm intervals were merged.
Data
Blue color highlights valve endothelial cells forming a disc inside the vessel lumen; gray represents the vessel wall. Reconstruction was done using images of serial semithin sections (400 nm) through the developing valve.