Bioscience and Biotechnology Center
Group of Animal Organ Functions

ProfessorMasahiko Hibi
Axis formation and its linked neurogenesis
Associate ProfessorTakashi Shimizu
Development and function of cerebellar neural circuits
Assistant ProfessorHisashi Hashimoto
Development of neural crest-derived cells and medaka genetics
Laboratory HP
Masahiko Hibi Professor
Lab members

During early vertebrate development, the embryonic axes-dorso-ventral (DV), anterior-posterior (AP), and left-right (LR) - are established through a series of inductive signals that are followed by the concerted movements and differentiation of a group of cells. Our general interest is in learning how these body axes are established and how cells adopt their fates at the appropriate positions within these axes.

Axis formation

The dorsal organizer plays a major role in the process of axis formation. In amphibian and teleost fish embryogenesis, the program for dorsal organizer formation begins soon after fertilization. In these species, the dorsal determinants are initially localized to the vegetal pole, and subsequently transported to the dorsal side of the embryo. Although the molecular nature of the dorsal determinants has not been elucidated, the dorsal determinants activate the canonical Wnt pathway and thereby lead to the expression of the genes involved in the induction of the dorsal organizer. The dorsal organizer generates secreted signaling molecules that participate in the generation of the DV axis in the mesoderm and endoderm, as well as the formation of the neuroectoderm. Our research aims include elucidation of the mechanisms by which the dorsal organizer is established and regulates axis formation. To address these questions, we are seeking the molecular identity of the dorsal determinants, and trying to identify novel molecules that are involved in the formation and function of the dorsal organizer.

Cerebellum development

The cerebellum functions in the control of smooth and skillful movements. It is also implicated in a variety of cognitive and emotional functions. The cerebellum integrates sensory and predictive inputs, which include proprioception and information associated with motor commands, to elicit precise motor control and higher cognitive/emotional functions. Because the structure of the cerebellum is conserved between teleosts and mammals, we believe the zebrafish cerebellum to be a good system for studying all the steps involved in cerebellar neurogenesis and the formation of the neural circuitry, with the strong expectation that the findings will be applicable to mammals. We have determined the cell types and neural tracts in the zebrafish cerebellum using molecular markers and transgenic lines. We have also isolated mutations affecting cerebellar neuronal development and the formation of neural tracts. Using genetics and in vivo imaging, we hope to reveal the molecular mechanisms that control the development and maintenance of cerebellar neurons, and the neural circuits in the zebrafish and medaka cerebellum, which will serve as a model system for understanding vertebrate higher brain structure.

We are also studying function of cerebellar neural circuits in zebrafish and medaka using calcium imaging, optogenetics, and leading-edge techniques for genetic manipulation.

Medaka genetics

Many medaka resources have been developed in our fish facility. Most of them are natural mutants with various abnormal phenotypes in pigmentation, morphology, and behavior. Some of them can be fish models for studies of certain human diseases. Medaka has four types of pigment cells. The pigment cells are derived from the common progenitor cells called the neural crest cells, as in human. Using the medaka resources, we are studying molecular mechanisms that control specification of the pigment cells from the neural crest cells.

Fig. 1.

The maternal-effect mutant tokkaebi displays a completely ventralized phenotype. Nuclear accumulation of b-catenin is affected in a tokkaebi embryo.

Fig. 2.

Development of cerebellar neurons in zebrafish larvae at 5 days post fertilization. Purkinje neurons (green) receive axons of granule cells (magenta) in wild type. Loss and abnormal extension of granule cell axons are observed in gazami and shiomaneki mutants, respectively.


  1. Tanabe et al. J. Neurosci. 30, 16983-16992, 2010.
  2. Nagao et al. Dev. Biol. 347, 53-61, 2010.
  3. Shimizu et al. Development 137, 1875-1885, 2010.
  4. Kani et al. Dev. Biol. 343, 1-17, 2010.
  5. Nojima et al. Development 137, 923-933, 2010.
  6. Bae et al. Dev. Biol. 330, 406-426, 2009.
  7. Hashimoto et al. PLoS One 4, e6299, 2009.
  8. Shimizu et al. Development 133, 4709-4719, 2006.
  9. Hirata et al. Development 133, 3993-4004, 2006.
  10. Muraoka et al. Nat. Cell Biol. 8, 329-340, 2006.
  11. Hirata et al. Development 133, 1433-1443, 2006.
  12. Bae et al. Development 132, 1375-1385, 2005.
  13. Hashimoto et al. Development 131, 1741-1753, 2004.
  14. Yabe et al. Development 130, 2705-2716, 2003.
  15. Bae et al. Development 130, 1853-1865, 2003.