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ゼブラフィッシュを用いた腸神経系傷害後の再生機構の解明
大野 真理愛 / Maria Ohno:1 堀内 奈津美 / Natsumi Horiuchi:1 川上 浩一 / Koichi Kawakami:2 二階堂 昌孝 / Masataka Nikaido:1 八田 公平 / Kohei Hatta:1 Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Japan The enteric nervous system (ENS) is the largest part of the peripheral autonomic nervous system. It controls the gastrointestinal functions such as peristaltic movement and secretion of hormones basically independently from the central nervous system. Therefore, it is often called the second brain. Because of the essential roles of the ENS, congenital loss of the ENS often causes fatal diseases. To recover the lost neurons in such diseases, regeneration of neurons from transplanted stem cells is supposed a promising method, and for this it is informative to understand mechanisms controlling regeneration of the ENS in other animals where it happens. Zebrafish is known as a good vertebrate model to study the regeneration of heart, hair cell, retina and so on. Here, we used it to study the regeneration mechanisms of the ENS. First, we showed that enteric neurons and axons of 10~15-day larva started to regenerate within 1 day after ablation, and that neurons were recovered to 80 % of neurons in untreated area by 10 days after ablation. We also found 73 % of regenerated neurons were BrdU-positive, and the remaining was BrdU-negative. Further immunostaining with neural stem cell marker, Sox10, showed increase of BrdU/Sox10-double positive cells in injured area. We conclude that enteric neurons in zebrafish are regenerated both from the neural precursors without cell division and from the stem cells via cell division. Moreover, Sox10-positive stem cells can proliferate in response to injury to produce neurons. |