Understanding children's brain development
An infant's brain undergoes dynamic changes and eventually matures into a fully developed circuitry. During this process, synapses are formed between billions of neurons. Our works in the past revealed synapse organizers, such as Cbln1, are critical for synapse formation within local circuits in unique brain areas (Ito-Ishida, JNS, 2008; Ito-Ishida, Neuron 2012). However, we know much less about the developmental mechanisms that regulate larger circuits consisting of multiple and distant brain regions. Our team uses multidisciplinary approaches including molecular/ cellular biology, viral tracing, and functional calcium imaging, to clarify how larger circuits form and mature during postnatal development. We are particularly interested in how the connection is established between the cerebellar and cerebral cortex because this connectivity is highly implied in developmental disorders such as autism.
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Changes in the molecules that support brain development lead to a variety of pediatric neurological disorders. As a first step in understanding the complex pathophysiology of developmental disorders, our laboratory focuses on a monogenic disorder, Rett syndrome, which has a clear relationship between cause and disease. Using mouse models, our previous work identified critical roles of inhibitory neuronal subtypes in the pathophysiology of Rett syndrome (Ito-Ishida, Neuron, 2015). More recently, we showed functional significance of MeCP2 for the structural integrity of heterochromatin in neurons (Ito-Ishida, Nature Neuro, 2018; JNS, 2020). However, much remains unclear as to what abnormalities in the neural circuit cause the specific symptoms associated with this neurological disorder.
The new team will tackle this problem by applying the knowledge gained through research on normal brain development and multifaceted experimental methods that connect molecules and behavior. Taking advantage of an excellent environment at RIKEN CBS, we hope to achieve our goal by conducting collaborative and interdisciplinary projects.
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Neurodevelopmental disorders ：
basic mechanisms to therapeutic strategy