Biology subjects

Selimi, F.

Publications and source records attributed to Selimi, F..

6 recordsLinked to original sources

bioRxiv2026

Neuronal excitability coordinates the timing of input/output circuit assembly

How neurons coordinate the timing of migration, differentiation and synaptic integration with their specific inputs and outputs remains poorly understood. Here we show that granule cells, the brain's most numerous neuronal population, establish immature synaptic contacts on their output targets, the cerebellar Purkinje cells, well before completing their radial migration and becoming innervated by their mossy fiber inputs. This happens at a specific stage when granule cells reach the molecular layer and begin expressing presynaptic markers and a specific NMDA receptor subtype. Chemogenetic silencing of these migrating, differentiating granule cells shows that their excitability is required for output synapse maturation. Thus neuronal activity coordinates the timing of input and output synapse development. This mechanism might underlie GRIN2B-related pathologies that include autism spectrum disorders.

developmental biology↗

bioRxiv2023

A molecularly-defined non-redundant subpopulation of OPCs controls the generation of myelinating oligodendrocytes during postnatal development.

Oligodendrocyte precursor cells (OPCs) are a class of glial cells that uniformly tiles the whole central nervous system. They play several key functions across the brain including the generation of oligodendrocytes and the control of myelination. Whether the functional diversity of OPCs is the result of genetically defined subpopulations or of their regulation by external factors has not been definitely established. We discovered that a subpopulation of OPCs found across the brain is defined by the expression of C1ql1, a gene previously described for its synaptic function in neurons. This subpopulation starts to appear during the first postnatal week in the mouse brain. Ablation of C1ql1-expressing OPCs in the mouse is not compensated by the remaining OPCs, and results in a massive lack of oligodendrocytes and myelination in many brain regions. Therefore, C1ql1 is a molecular marker of a functionally non-redundant subpopulation of OPCs, which controls the generation of myelinating oligodendrocytes.

neuroscience↗

bioRxiv2023

Mapping and targeting of C1ql1-expressing cells in the mouse

The C1Q complement protein C1QL1 is highly conserved in mammals where it is expressed in various tissues including the brain. This secreted protein interacts with Brain-specific Angiogenesis Inhibitor 3, BAI3/ADGRB3, and controls synapse formation and maintenance. C1ql1 is expressed in the inferior olivary neurons that send projections to cerebellar Purkinje cells, but its expression in the rest of the brain is less documented. To map C1ql1 expression and enable the specific targeting of C1ql1-expressing cells, we characterized a knockin mouse model expressing the Cre recombinase under the control of C1ql1 regulatory sequences. We characterized the capacity for Cre-driven recombination in the brain and mapped Cre expression in various neuron types using reporter mouse lines. Using an intersectional strategy with viral particle injections, we show that this mouse line can be used to target specific afferents of Purkinje cells. As C1ql1 is also expressed in other regions of the brain, as well as in other tissues such as adrenal glands, placenta, colon and testis, our mouse model is a useful tool to target C1ql1-expressing cells in a broad variety of tissues.

neuroscience↗

bioRxiv2023

Stepwise molecular specification of excitatory synapse diversity on a target neuron

Brain function relies on the generation of a large variety of morphologically and functionally diverse, but specific, neuronal synapses. Here, we show that, initially, synapse formation on a common target neuron, the cerebellar Purkinje cells, involves a presynaptic secreted protein common for all types of excitatory inputs. The molecular program then evolves only in one of the inputs with the additional expression of a combination of presynaptic secreted proteins that specify the mature pattern of connectivity on the target. These results show that some inputs actively and gradually specify their synaptic molecular identity while others rely on the "original code". Thus, the molecular specification of excitatory synapses, crucial for proper circuit function, is acquired in a stepwise manner during mouse postnatal development and obeys input-specific rules.

neuroscience↗

bioRxiv2019

SUSD4 Controls Activity-Dependent Degradation of AMPA Receptor GLUA2 and Synaptic Plasticity

Fine control of protein stoichiometry at synapses underlies brain function and plasticity. How proteostasis is controlled independently for each type of synaptic protein in a synapse-specific and activity-dependent manner remains unclear. Here we show that SUSD4, a complement-related transmembrane protein, binds the AMPA receptor subunit GLUA2 and controls its activity-dependent degradation. Several proteins with known roles in the regulation of AMPA receptor turnover, in particular ubiquitin ligases of the NEDD4 subfamily, are identified as SUSD4 binding partners. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function of Susd4 in the mouse prevents long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. Our findings reveal that activity-dependent synaptic plasticity relies on a transmembrane CCP domain-containing protein that regulates the degradation of specific substrates. This mechanism potentially accounts for the role of SUSD4 mutations in neurodevelopmental diseases.

neuroscience↗

bioRxiv2018

Expression and role of Galectin-3 in the postnatal development of the cerebellum

Many proteins initially identified in the immune system play roles in neurogenesis, neuronal migration, axon guidance, synaptic plasticity and other processes related to the formation and refinement of neural circuits. Although the function of the immune-related protein Galectin-3 (LGALS3) has been extensively studied in the regulation of inflammation, cancer and microglia activation, little is known about its role in the development of the brain. In this study, we identified that LGALS3 is expressed in the developing postnatal cerebellum. More precisely, LGALS3 is expressed by cells in meninges and in the choroid plexus, and in subpopulations of astrocytes and of microglial cells in the cerebellar cortex. Analysis of Lgals3 knockout mice showed that Lgals3 is dispensable for the development of cerebellar cytoarchitecture and Purkinje cell excitatory synaptogenesis in the mouse.

neuroscience↗