[Molecular mechanism of brain regeneration and reconstruction of dopaminergic neural network in planarians].
Recently, planarians have received much attention because of their contributions to research on the basic science of stem cell systems, neural regeneration, and regenerative medicine. Planarians can regenerate complete organs, including a well-organized central nervous system (CNS), within about 7 days. This high regenerative capacity is supported by pluripotent stem cells present in the mesenchymal space throughout the body. Interestingly, planarians can regenerate their brain via a molecular mechanism similar to that of mammalian brain development. The regeneration process of the planarian brain can be divided into five steps: (1) anterior blastema formation, (2) brain rudiment formation, (3) brain pattern formation, (4) neural network formation, and (5) functional recovery, with several kinds of genes and molecular cascades acting at each step. Recently, we have identified a planarian tyrosine hydroxylase (TH) gene, a rate-limiting enzyme for dopamine (DA) biosynthesis, and produced TH-knockdown planarians by the RNA interference technique. Studies of TH-knockdown planarians showed that DA has an important role of the modification in behavioral movement in planarians. Using monoclonal anti-planarian TH antibody, we also found that dopaminergic neurons are mainly localized in the planarian brain. When the planarian body was amputated, newly generated TH-immunopositive neurons were detected in the anterior region at day 3 of regeneration (i.e., the period of neural network formation), and the TH-immunopositive axonal and dendritic neural network in the CNS was reconstructed during day 5-7 of regeneration. In this article, recent advances in elucidating the molecular mechanism of planarian brain regeneration and dopaminergic neurons are reviewed, and its future prospects for contribution of this system to basic science and medical science research are described.
Nishimura
Kaneyasu
K
Department of Neurobiology, Kyoto Pharmaceutical University, 5 Nakauchi cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Kitamura
Yoshihisa
Y
Agata
Kiyokazu
K
D000818:Animals; D001921:Brain / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D010932:Planarians / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000502:physiology*
D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine