Laboratory of Systems Neurobiology and Medicine

Research Projects

Research Projects

Axon/dendrite formation, neuronal polarization and migration


DThe basic function of neurons is to receive signals, integrate them and transmit them to the next neuron. Thus, neurons can function as semiconductors in the brain. Neuronal polarity plays an essential role for this function. Namely, most of neurons form a single axon and multiple dendrites. Dendrites receive signals from outside, while an axon output signals. Then a signal flow arises from dendrites via cell body to the axon. How neurons acquire neuronal polarity? Our lab investigates the mechanism for axon/dendrite formation and neuronal polarization, focusing on shootin and singar (Toriyama et al., 2006; Mori et al., 2007), as well as their interacting proteins. We are also analyzing how neurons polarize in order to migrate.

Generation of mechanical forces for neurite outgrowth and migration


Animals move and change their shape, using force generated by muscles. How cells do so? Actin polymerizes near the leading edges of neurite tips and migrating cells. Our studies showed that shootin1 interacts with both the polymerizing actin filaments and L1-CAM at neurite tips, thereby generating traction force for neurite outgrowth (Shimada et al., 2008). We are currently analyzing such linker molecules (“Clutch” molecules) to understand the molecular mechanisms for force generation for neurite outgrowth and cell migration.

Sensing of cellular length and size


Correct control of size and morphology is essential for cells to function properly. In contrast to the progress in understanding the molecular signals that change cell morphologies, the manner in which cells check their size and length to regulate their morphology is poorly understood. Recently we found that shootin1 accumulates in neurite tips in a neurite length-dependent manner (Toriyama et al., 2010; Inagaki et al., 2010). Thus, morphological information, neurite length, is translated into a molecular signal (shootin1 concentration in neurite tips). Live cell imaging combined with mathematical analyses further demonstrated that the neurite length-dependent shootin1 accumulation is quantitatively explained by its anterograde transport and retrograde diffusion.

Crux of biological morphogenesis: symmetry breaking


Our model neuron breaks symmetry as in the case of cultured neurons (Toriyama et al., 2010). The validity of the model was supported by 15 agreements between the behaviors of the model and cultured neurons. (LINK)

Biological systems self-organize their simple shape into more complicated ones in a universe that continuously increase disorder (entropy). Symmetry breaking is an essential step of such miraculous biological morphogenesis. As an example, neurons break their symmetry by elongating a single long axon and multiple short dendrites (Craig and Banker, Annu Rev Neurosci 17:267-31, 1994; Yamasaki et al, J Neurosci 30:15221-7, 2010): symmetry breaking is the initial step of neuronal polarity formation. One advantage of neurons over other types of cells is that their morphology can be described in simple terms using a small number of variables for neurite length (see left). Using a combination of quantitative live cell imaging and mathematical modeling, we are analyzing the mechanisms involved in neuronal symmetry breaking. Our data suggest that the abovementioned length-dependent shootin1 accumulation and shootin1-dependent neurite outgrowth constitutes a positive feedback loop that amplifies stochastic fluctuations of shootin1 signals, thereby leading to spontaneous neuronal symmetry-breaking (Toriyama et al., 2010; Inagaki et al., 2010).

Contact us

Naoyuki Inagaki, MD, PhD

Graduate School of Biological Sciences
Nara Institute of Science and Technology

Ikoma 630-0192, Japan (access map)
Tel: +81-743-72-5466
Email: ninagaki(a)