Laboratories

Developmental Biomedical Science

Assoc. Prof. Sasai
Associate Professor
Noriaki SASAI
Assistant Professor
Akiko NISHI-HORI
Labs HP
http://bsw3.naist.jp/sasai/

Outline of Research and Education

One of the central questions of classical developmental biology is to understand how a limited number of genes produce a diversity of cell types. The developing central nervous system is composed of a number of different cell types, and we seek to elucidate the molecular mechanisms leading to this diversity by employing chick and mouse embryos as model organisms.

We are also interested in the homeostasis of functional neurons. We have been utilising model mice that have been shown to develop particular inherited retinal diseases, and propose novel therapeutics for these related dystrophies.

Overall, our research program aims to be influential in cell and developmental biology and will furthermore be scientifically and technically cross-disciplinary across basic biology and clinical biomedical sciences.

Major Research Topics

Transition of the intrinsic characteristics of 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 precisely assigned. This pattern formation is mainly governed by a handful of extracellular molecules including BMP, Wnt and Sonic Hedgehog (Shh). These molecules are collectively called morphogens, and induce different neuronal subtypes in a graded manner. On the other hand, the intrinsic characteristics of 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 signaling pathway

There are many unique aspects of the intracellular signaling 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 in maintaining established photoreceptor cells, and that 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.

References

  1. Dellett et al., Investigative Ophthalmology and Visual Science, 56, 164-176, 2015
  2. Sasai et al., PLOS Biology, 12, e1001907, 2014
  3. Sasai et al., WIREs Developmental Biology, 1, 753-772, 2012
  4. Dessaud et al., PLOS Biology, 8, e1000382, 2010
  5. Ribes et al., Genes and Development, 24, 1186-1200, 2010
  6. Sasai et al., Cell, 133, 878-890, 2008
Fig. 1 (A) The cross section of the trunk neural tube. The neural tube is divided into at least 13 subdomains along the dorsal-ventral axis. (B) The floor plate and the p3 interneuron progenitor domains can be separated by immunohistochemistry. (C,D) The phenotype of the neural tube upon forced expression of Shh. The neural progenitor cells tend to differentiate into the floor plate cells (C), while they differentiate into the p3 cells when Shh is overexpressed at the late stage (D). This finding suggests that the neural progenitor cells respond to the same signal differently over time.
Fig. 1 (A) The cross section of the trunk neural tube. The neural tube is divided into at least 13 subdomains along the dorsal-ventral axis. (B) The floor plate and the p3 interneuron progenitor domains can be separated by immunohistochemistry. (C,D) The phenotype of the neural tube upon forced expression of Shh. The neural progenitor cells tend to differentiate into the floor plate cells (C), while they differentiate into the p3 cells when Shh is overexpressed at the late stage (D). This finding suggests that the neural progenitor cells respond to the same signal differently over time.
Fig. 2 The Shh signalling pathway involves a lot of interacting proteins.
Fig. 2 The Shh signalling pathway involves a lot of interacting proteins.
Fig. 3 Eye phenotype in the Prominin-1 (Prom1) deficient mice. The outer segments are degenerated (A,B), and Rhodopsin proteins are misplaced in the photoreceptor cells of the Prom1-knockout eyes (C,D).
Fig. 3 Eye phenotype in the Prominin-1 (Prom1) deficient mice. The outer segments are degenerated (A,B), and Rhodopsin proteins are misplaced in the photoreceptor cells of the Prom1-knockout eyes (C,D).
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