石嶺 久子

Toxic compounds from the mother's diet and medication in addition to genetic factors and infection during pregnancy remain risks for various congenital disorders and misbirth. To ensure the safety of food and drugs for pregnant women, establishment of an in vitro system that morphologically resembles human tissues has been long desired. In this study, we focused on dorsal mesoderm elongation, one of the critical early development events for trunk formation, and we established in vitro autonomous elongating tissues from human induced pluripotent stem cells (hiPSCs). This artificial tissue elongation is regulated by MYOSIN II and FGF signaling, and is diminished by methylmercury or retinoic acid (RA), similar to in vivo human developmental disabilities. Moreover, our method for differentiation of hiPSCs requires only a short culture period, and the elongation is cell number-independent. Therefore, our in vitro human tissue elongation system is a potential tool for risk assessment assays for identification of teratogenic chemicals via human tissue morphogenesis.

Paroxysmal dystonic choreoathetosis (PDC) is thought to be a hereditary channelopathy mapped to chromosome 2q32-36. By means of linkage analysis on a large Japanese family, we have narrowed the PDC locus that contains 32 candidate genes. Here, we report that a heterozygous mutation (A7V) in one of such genes, myofibrillogenesis regulator 1 (MR-1), is responsible for PDC in the Japanese family. This is consistent with the finding in American PDC families. We further report that there are several other polymorphisms in MR-1 in the Japanese PDC family. To characterize MR-1, we generated specific antibodies against MR-1 and performed the immunohistochemical analysis in rat brain. The results of the MR-1 localization will be discussed. Similar to other channelopathies such as epilepsy and migraine, PDC is characterized by involuntary movement attacks, and is presumed to be induced by abnormalities of ion channels. Although MR-1 may be associated with some ion channels, its physiological functions remain unclear. Further characterization of MR-1 including its molecular function and relationship to ion channels, may facilitate not only to understand pathophysiology of PDC, but also to develop effective therapies for paroxysmal neurological disorders. [J Physiol Sci. 2006;56 Suppl:S157]

文字認識やパターン認識などに用いられる画像処理技術である二値化処理と細線化処理を適用することで、分散培養・組織培養における、枝分かれし、曲線的で複雑に伸長する神経突起長をより正確に計算する方法を組み込んだソフトウェア(Mneurites)を創作した。後根神経節の分散培養を用いてこの方法を従来の方法と比較し、より正確な結果を得ることができた。らせん神経節や後根神経節の小片培養における神経突起の計測を行った。従来困難であった小片培養においてもこの方法が適用できた。神経の発生、再生などの仕組みを解析する上で非常に有用であることが示唆された。