Prof. Hiroshi Kawasaki

In the late Larry Katz's lab at Duke/HHMI, we fabricated a custom-made ferret microarray and found several molecules with intriguing expression patterns (Journal of Neuroscience 2004). We uncovered that FoxP2 is selectively expressed parvocellular neurons in the ferret and monkey LGN (Cerebral Cortex 2013). Using these molecules, we examined the mechanisms underlying visual system development (Neuroscience 2009, PLoS One 2010).

To investigate molecular mechanisms in ferrets, we recently established a method to manipulate gene expressions using in utero electroporation (Molecular Brain 2012). This is the first application of in utero electroporation to higher mammals, and is useful to express transgenes into the OSVZ (Biology Open 2013). By combining in utero electroporation and the CRISPR/Cas9 system, we established gene knockout methods in the ferret cerebral cortex (Cell Reports 2017). Using our methods, we have uncovered the molecular mechanisms of cortical folding (i.e. gyrification). We found that FGF signaling, Tbr2 transcription factor, upper layer neurons are crucial for cortical folding (Cell Reports 2017, eLife 2017, Scientific Reports 2015, 2016). Furthermore, we made a ferret model of polymicrogyria and analysed its pathophysiology (Scientific Reports 2015, Human Molecular Genetics 2017, 2018).

Our techniques using ferrets could help our mechanistic understanding of brain development and diseases in higher mammals

Sensory systems using mice
We are also working on the mechanisms of brain development using mice.

It seems reasonable to say that the most drastic environmental changes in our entire life is birth from mothers. Before birth, embryos are protected in mothers' body, and receive oxygen and nutrients automatically. In contrast, immediately after birth, newborn babies receive environmental sensory inputs from the outside and have to start to use their brains to survive. Nevertheless, the roles of birth in brain development are not well understood. Recently, we found that the birth is the trigger to make neuronal circuits in the somatosensory and visual systems via serotonin signaling (Developmental Cell 2013). Further, we also found that behavioral maturation is also regulated by birth (Molecular Brain 2014).
Using the somatosensory cortex, we uncovered novel axonal trajectories of layer 2/3 neurons in the mouse barrel cortex, and named this trajectories "barrel nets" (Journal of Neuroscience 2010, Neuroscience 2012). Using barrel nets, we found that the cell adhesion molecule cadherin is crucial for making local neuronal circuits in the cerebral cortex (Cerebral Cortex 2015)