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SinGly

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Glycobiology of synaptic pruning in a developing brain

Effective neuron-microglial communication is a prerequisite to achieve the final connectome. It is mediated by both the formation of new synapses and selective removal of unnecessary connections through synaptic pruning. Recent ev... ver más

31/10/2022

Vilniaus universit...

146K€

Presupuesto del proyecto: 146K€

Líder del proyecto

VILNIAUS UNIVERSITETAS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-10-31

MSCA-IF-2019: Individual Fellowships

I+D

Cerrada hace 5 años

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1 Participantes

Vilniaus universitetas

146.11K€ | Lider

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Duración del proyecto: 30 meses Fecha Inicio: 2020-04-14
Fecha Fin: 2022-10-31

Líder del proyecto

VILNIAUS UNIVERSITETAS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 146K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Effective neuron-microglial communication is a prerequisite to achieve the final connectome. It is mediated by both the formation of new synapses and selective removal of unnecessary connections through synaptic pruning. Recent evidences suggest that superfluous connections are eliminated by microglia. Almost 70% of the connections are lost in a primate cortex within six months of life. But what drives this selective elimination of so many synapses is a million-euro question. Identifying neuronal signals that differentiate weak synapses from the strong ones is an emerging frontier in cellular neuroscience. Several eat-me signals in synaptic pruning have been identified, but spare-me signals that limit phagocytic elimination of synapses are yet to be explored. Sialic acids on neuronal glycocalyx acts as spare-me signal and prevents microglial phagocytosis through Siglec receptors. Aberrant regulation of sialic acid caused neuronal loss and embryonic lethality. It is also becoming evident that sialic acid plays a key role in neurodevelopment, but the cellular and molecular mechanisms by which it regulates neurodevelopment is yet to be explored. This makes sialic acid an ideal candidate to evaluate its role in neurodevelopment. Hence, we aim to interrogate whether sialidases, glycocalyx recognizing proteins are developmentally regulated and also to define sialic acid’s role in synaptic pruning during neurodevelopment. We propose to implement gene, protein expression and metabolic profiling studies to investigate whether sialidases and glycocalyx recognizing proteins are developmentally regulated. Also, we will use fluorescent azido sugars in ex vivo cultures to visualise how sialic acid regulates synaptic pruning during neurodevelopment using superresolution STED microscopy. This paves a path to identify cellular and molecular mechanisms by which glycocalyx composition defines neuron-microglia interactions and thus circuit refinement through synaptic pruning.

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