河崎洋志

We are interested in the molecular mechanisms underlying brain formation during development. How such complex, fine and beautiful structures are formed from single fertilized eggs? Especially, we are focusing on the following three points.


The first point is the identities of neurons. One feature of our central nervous system is the diversity of neuronal identities. We are interested in how neuronal identities are determined during development in mammalian brains. In the human brain, there are about 100 billion neurons, whereas we have only 30,000 genes. It is mysterious how the identities of each 100 billion neurons are precisely determined by only a small number of genes. To examine this point, we previously established in vitro culture system that triggers selective differentiation of mouse and primate ES cells into neurons (Neuron 2000; Nature Neuroscience 2005; PNAS 2002, 2003, 2006). This SDIA method enabled us to examine the mechanisms of mammalian neuronal differentiation processes, which occur in utero, in culture dishes! Furthermore, using our SDIA method, we succeeded to make dopaminergic neurons from mouse and primate ES cells in vitro (Neuron 2000, PNAS 2002). Dopaminergic neurons made in vitro using our SDIA method could be applicable for transplantation therapy for Parkinson’s disease (J Clin Invest 2005).


Our second point is neuronal connections. Once neuronal identities are determined, precise neuronal connections are made by genetic programs and neuronal activities. We are examining the molecular mechanisms underlying neuronal circuit formation using visual and somatosensory systems as model systems. We examined the mechanisms underlying the termination of whisker-lesion induced barrel structural plasticity (Mol Cell Neurosci 2008). Our results suggest that the visual and somatosensory systems might utilize distinct molecular mechanisms to regulate the termination of the developmental plasticity. We also found novel axonal trajectories of layer 2/3 neurons in the mouse barrel cortex, and named this trajectories “barrel nets” (Journal of Neuroscience 2010).


The third point we are interested in is the brain of higher mammals. Although mice are commonly used to investigate the molecular mechanisms underlying the formation of the central nervous system, mice do not have several interesting structures that higher mammals have. For examples, ocular dominance columns in the visual system are missing in mice, and it is therefore difficult to investigate the mechanisms responsible for the formation of these structures. To overcome this limitation, we started to use ferrets, which have been commonly used for anatomical and physiological experiments. In the late Dr. Larry Katz lab, we fabricated custom-made ferret microarray and found several molecules with intriguing expression patterns (Journal of Neuroscience 2004, Cerebral Cortex 2012). Using these molecules, we examined the mechanisms underlying visual system development (Neuroscience 2009, PLoS One 2010). Our results using ferrets could help our mechanistic understanding of brain development in higher mammals including humans.


In addition, we believe that technical advances would be important for scientific discoveries, and are therefore interested in technical improvement. Recently, we made a new technique for simulatneous visualization of multiple neuronal properties with single-cell resolution in the living rodent brain using in utero electroporation (Mol Cell Neurosci 2011). Combining this technique PASME and 2-photon in vivo imaging, we can visualize, for example, spines and their presynaptic inputs derived from surrounding neurons. In addition, we made new immunostaining protocols using cholesterol-specific detergent digitonin. Our immunostaining protocol enables us to perform double-labeling using immunohistochemistry and DiI neuronal tracing (J. Neurosci. Methods 2008). Using similar protocol, we made a novel immunostaining protocol using anti-lipid antibody (J. Neurosci. Methods, 2009).

Molecular and Developmental neuroscience 

Hiroshi Kawasaki

Department of Molecular and Systems Neurobiology

Graduate School of Medicine

The University of Tokyo

visual system, somatosensory system, ferret

neuroscience, neurobiology