The research in the Kamiyama laboratory is aimed at identifying the general principles of neural circuit assembly. To carry out the research, we have been developing a variety of imaging toolkits.
Deciphering the contact-signaling code of neural morphogenesis in establishing neural circuits
Our brain consists of billions of neurons connected into circuits. Knowing how this neuronal circuitry is assembled is not only the central question of brain development studies, but also the key to understand the pathogenesis of neurodevelopment disorders such as Autism spectrum disorder, Down syndrome, Fragile X syndrome. This assembly requires a complex coordination of developmental events. After cellular differentiation to achieve their proper fate, newly generated neurons extend their projections. These projections are further guided to their proper target regions by three different types of signals: cytoplasmic (e.g. axon-dendrite specification), diffusive (e.g. axon guidance) and cell-cell contact signals (e.g. synaptic connection). In particular, the contact signals spatially position neural morphological features with a remarkable precision, which can’t be achieved by either the cytoplasmic or the diffusive signals. A perfect example is given by our recent work that revealed molecular mechanisms underlying the specification of dendrite growth site in the Drosophila central nervous system (CNS). Using the aCC motoneuron as a model system because of its highly stereotyped and simple morphological features, we have discovered that the positional cue of aCC dendrite outgrowth comes from its contact with a partner MP1 neuron, and that this communication is mediated by Down syndrome cell-adhesion molecule (Dscam1) signaling. Our findings provide the first mechanistic evidence for Dscam1 inter-neural signaling, as opposed to its well-known functions in intra-neuron signaling of dendrite-dendrite repulsion.
Directed by our recent findings, our long-term objective is to decipher the contact-signaling code of neural morphogenesis in neural circuit assembly. Our research is being focused on deeply understanding the general mechanisms of Dscam1 inter-neural signaling during CNS morphogenesis. At the same time, we are developing two imaging toolkits to enable the systematic study of contact-signaling pathways, including a Drosophila library of fluorescent tagged neuron adhesion molecules to map a contact signaling pathways to specific morphological features, as well as a contact-triggered expression system to identify contact partner cells of a given neuron.
Leonetti, MD., Sekine, S., Kamiyama, D*., Weissman, SJ*., and Huang, B*. (2016). A scalable strategy for high-throughput GFP tagging of endogenous human proteins. Proc. Natl. Acad. Sci. USA, 113, E3501-E3508. (* co-corresponding authorship) [link]
Kamiyama, D*., Sekine, S*., Barsi-Rhyne, B., Hu, J., Chen, B., Gilbert, L., Ishikawa, H., Leonetti, MD., Wallace, F., Weissman, J., and Huang, B. (2016). Versatile protein tagging in cells with split fluorescent protein. Nat Commun 7, 111046. (* shared first authorship) [link]
Kamiyama, D*., McGorty, R., Kamiyama, R., Kim, M., Chiba, A., and Huang, B*. (2015). Specification of dendritogenesis in Drosophila aCC motoneuron by membrane-enrichment of Pak1 through Dscam1. Developmental Cell 35, 93-106. (* co-corresponding authorship) [link]
Kamiyama, D*., and Huang, B*. (2012). Development in the STORM. Developmental Cell 23, 1103-1110. (* co-corresponding authorship) [link]
Kamiyama, D., and Chiba, A. (2009). Endogenous activation patterns of Cdc42 GTPase within Drosophila embryos. Science 324, 1338-1340. [link]