Analysis of cell migration and axonal pathfinding of trigeminal motor neurons in zebrafish
of the molecules regulate each step of the development of motor neuron is one
of the fundamental questions of the developmental neurobiology. However, these
mechanisms are largely unknown. Therefore, using the anterior and posterior
trigeminal motor neurons (Va, Vp) and facial motor neurons (VII) as a model
systems, we performed the ENU-induced mutant screening on 1816.5 genomes and
isolated 10 mutant strains which shows the defects in each step of the
development of these motor neurons. In zebrafish, the
Vp motor neurons consist of two populations which are distinguished in birth
time and birth place in rhombomere 3 (r3).
Time-lapse imaging revealed that the late born (48hpf) population which is born
in close to the midline migrates laterally and passing through the early born
(36hpf) population locate in the lateral part of r3. The freeze frame (fzf) embryos are specifically defective in
the late born population and perturbation of the inside-out migration resulted
in the failure to make the motor nucleus of Vp. The inside-out cell migration
plays an important role to establish the laminar structures of CNS such as
cerebral cortex. We hope to reveal the novel cell migration mechanisms through
the analysis of this mutant.
The growth pathways of the Vp motor neurons to
their specific target muscles in lower jaw region consist of four steps, 1)
defasciculation from the common pathway which is shared by both motor and
sensory axons and growth toward their specific target muscles 2) bifuracation
and growth toward contralateral target muscles closing the midline 3) closing
the boundary between the 1st and 2nd branchial arch and
4) growth on the 2nd branchial arch target muscles. Such a stepwise
control of the growing axons from the main common pathway to their own specific
targets are observed in the various aspects in the developing CNS, and are
expected to be regulated by various types of molecular interactions. We have
isolated 8 mutants which shows the specific defects categorized into this four
steps. Now we are doing the analysis of these mutants and try to understand
these phenomena from the point of view of molecular interaction.
How the “living things” maintain themselves may be very simple, but nobody answered question. I joined this field with hope that someday we are able to answer this question.
My main theme is the analysis of the CNS defects in zebrafish mutant embryos. I am surprised deeply not only with the distinctive phenotype of the mutant embryos but also with the fact that these mutants can still maintain their own stereotypically deformed structures in spite of the lack of important genes. I think the mechanisms that enable individuals to adopt themselves to new genetic environments are the fundamental for life to be able to hand over their life to the next generation despite the constant reorganization of their genome.