Yuasa Shigeki, Hattori Kotaro, Yagi Takeshi
Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Neuroreport. 2004 Apr 9;15(5):819-22. doi: 10.1097/00001756-200404090-00016.
Fyn tyrosine kinase is involved in the tyrosine-phosphorylation of Disabled-1 in the Reelin signaling pathway, and absence of Fyn is expected to result in a reeler-like phenotype. Thus, this study investigated neocortical development in Fyn-deficient mice. Bromodeoxyuridine labeling revealed the under-migration of later-generated neurons despite the normal placement of earlier-generated neurons. Calbindin- and alpha-calcium/calmodulin-dependent protein kinase II-immunohistochemistry showed that layer II-III neurons were aberrantly stratified, but the neurons in the deeper layers showed little evidence of abnormality. Fyn was intensely expressed in the leading process of migratory cortical neurons generated in the later stage. These findings strongly suggest that Fyn is required for the migration of later-generated neurons, but that it is dispensable for the Reelin-dependent inside-out layer formation.
Fyn 酪氨酸激酶参与 Reelin 信号通路中Disabled-1 的酪氨酸磷酸化，预计 Fyn 的缺失会导致类似 reeler 的表型。因此，本研究调查了 Fyn 基因缺陷小鼠的新皮质发育情况。溴脱氧尿苷标记显示，尽管早期生成的神经元位置正常，但后期生成的神经元迁移不足。钙结合蛋白和α-钙调蛋白依赖性蛋白激酶 II 免疫组织化学显示，II-III 层神经元分层异常，但深层神经元几乎没有异常迹象。Fyn 在后期生成的迁移性皮质神经元的前端强烈表达。这些发现有力地表明，Fyn 是后期生成的神经元迁移所必需的，但对于 Reelin 依赖性的由内向外的层形成来说并非必需。
