Transition of the intrinsic characteristics of the neural progenitor cells during development and pattern formation
The neural tube is the embryonic tissue of the central nervous system, where a number of functional neurons are produced and are stereotypically assigned. This fate determination and pattern formation are governed by a relatively small number of inducing (secreted) factors including BMP, Wnt and Sonic Hedgehog (Shh). These molecules are collectively called morphogens, and induce different neuronal subtypes in a graded manner. In addition, the intrinsic characteristics of the neural progenitor cells change over time, and respond to the same inducing molecules differently. We are particularly interested in the relationship between the inducing activity and the cells' mode of response.
Detailed analysis of the Shh signalling pathway
There are many unique aspects of the intracellular signalling pathway induced by Shh. For instance, unlike other signalling molecules, the Shh pathway is introduced into the cells through the protrusive structure on the surface of cells, called the cilium. In addition, Shh target genes start to be expressed only after 6 hours, which is much slower than other signalling pathways. We attempt to chase the intracellular signalling molecules by labelling them at the single-protein level, and reveal the rate-limiting step of the signal, and will identify the regulators responsible for the speed of the signal. We will further modify the expression levels of these regulators and reveal the relationship between the speed of the signal and the construction of the high-dimensional structure.
Homeostasis of the functional cells
How functional cells are maintained is also an important question. We recently demonstrated that the membrane protein Prominin-1 (Prom1) has an essential role to maintain the established photoreceptor cells, and that the Prom1-deficient mice show severe retinal degeneration. In addition, our recent study suggests that Prom1 is involved in many more dystrophies in a number of other organs. We therefore aim to propose a novel therapeutic method by analysing these model mice.