Application of the whole embryo culture system to the study on the brain development

尽管近年来基因技术有了很大的进步，但哺乳动物脑发育的机制仍不完全清楚。其中一个原因是很难观察和操作在母亲子宫中发育的哺乳动物胚胎。本研究利用整个胚胎培养系统对小鼠胚胎脑进行了一些实验研究，以阐明脑发育的机制。我们已经研究了小鼠中脑在体内的发育，并获得的数据表明，神经细胞黏附分子L1和脑特有的硫酸软骨素蛋白多糖之间的分子相互作用参与了中脑多巴胺神经元的迁移(Kawano等人，1997年；Ohyama等人，1998年出版)。由于L1已被报道在体内与磷酸聚糖结合，这两个分子之间的分子相互作用可能在多巴胺神经元的迁移中发挥重要作用。在此基础上，我们用全胚胎培养系统将降解硫酸软骨素和抗体Ageinst L1的酶注射到E13小鼠胚胎的脑室内，并进行了脑组织学观察。该系统将成为研究哺乳动物大脑发育机制的有用工具。

In spite of the great advance of the gene technology in recent years, the mechanism of mammalian brain development is not fully known. One of the reasons is the difficulty in observing and manipulating mammalian embryos which develop in the mother's uterus. In the present study, some experimental manupilations were made to the embryonic mouse brain by using the whole embryo culture system to clarify the mechanisms of the brain development. We have already studied the in vivo development of the mouse midbrain and obtained the data which indicate that molecular interactions between neural cell adhesion molecules, L1 and a brain-specific chondroitin sulfate proteoglycan, phosphacan, are involved in the migration of mesencephalic dopamine-containing neurons (Kawano et al., 1997 ; Ohyama et al., 1998 in press). Since L1 have been reported to bind phosphacan in vivo, molecular interaction between the two molecules may play important roles in the migration of dopamine neurons. Based on these observation, we made microinjection of an enzyme which degrades chondrotin sulfate and antibody ageinst L1 into the ventricle of E13 mouse embryos using the whole embryo culture system, and exmined the brain histologically. This system will be a useful tool to study the developmental mechanism of the mammalian brain.