Regulators of Synapse Formation: Understanding the Molecular Mechanisms and its Dysregulation in Neurodevelopmental Disorders

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Background

Synapse formation is one of the key steps of brain development. The precise synaptic target selection and following pre- and postsynaptic differentiation are important for synaptic specificity and function. The correct establishment of synaptic connections during development is important for the proper functioning of the brain. Disruption of this process leads to a wide spectrum of neurodevelopmental disorders including autism, intellectual disability, and schizophrenia. Thus, understanding the molecular basis and regulatory mechanisms that govern synapse formation may be a prerequisite for developing therapeutic strategies.

Synapse formation is a multistep process mediated by cell adhesion molecules, secreted molecules, and cell-intrinsic regulatory components. Pre- and postsynaptic cell adhesion molecules called synaptic organizers play crucial roles in the synaptic target selection and differentiation at the initial step of synapse formation. The interaction of the synaptic organizer molecules generates bidirectional signals for pre- and postsynaptic specialization. However, the events that follow the interaction between these molecules are not well understood. The understanding of molecular mechanisms, including downstream signals, is a future challenge. How is the identity of synapses maintained in the mammalian brain composed of billions of neurons? The diversity of cell adhesion molecules and their splice variants has been proposed to confer specific identities on synaptic connection, which allows the precise pattern of connectivity between neurons. To understand the molecular basis for specification of each synaptic connection, we also need to know the molecular components of individual synapses, the spatial and temporal properties of these molecules, and how these molecular components function together.

Mutations in genes encoding synapse organizers and other adhesion proteins, and synaptic proteins have been identified to be causative or associated with neurodevelopmental disorders. Further identification of genetic causes and functional analyses of the mutations will greatly contribute to our understanding of pathogenic mechanisms of neurodevelopmental disorders, and facilitate the development of therapeutic strategies and drugs.

This Research Topic focuses on the molecular regulatory mechanisms that govern synaptic differentiation and specificity and on the pathogenic mechanisms involving such molecular components. The aim of this Research Topic is to gather recent advances in the field of synapse formation and its dysregulation in neurodevelopmental disorders. We welcome both original and review articles that provide insight into this field.

We welcome authors to submit articles focusing on, but not limited to the following topics:

・ Molecular mechanisms of synapse development including synapse formation, maturation, stabilization, and elimination

・ Pre- and postsynaptic molecular assemblies during synapse development

・ Regulatory mechanisms to specify the spatial and temporal aspects of synapse formation

・ Molecular pathogenic mechanisms of neurodevelopmental disorders caused by disruption of synapse development

Keywords: molecular, synapse, neurodevelopmental disorders

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