EphB2 tyrosine kinase-dependent forward signaling in migration of neuronal progenitors that populate and form a distinct region of the dentate niche.
EphB2 tyrosine kinase-dependent forward signaling in migration of neuronal progenitors that populate and form a distinct region of the dentate niche.
复制标题
DOI：
10.1523/jneurosci.6349-10.2011
复制
发表时间：
2011-08-10
期刊：
影响因子：
--
通讯作者：
Henkemeyer M
中科院分区：
文献类型：
--
作者：
Catchpole T;Henkemeyer M
齿状回（DG）是成熟大脑中干细胞驻留的两个区域之一，在整个成年期不断产生新的神经元。虽然许多研究都集中在DG在成人神经发生中的作用，但关于大脑的这个关键区域最初如何发育形成其独特的结构却知之甚少。我们在这里表明，小鼠EphB2受体酪氨酸激酶是胚胎/出生后发育的特定区域的DG称为外侧上锥叶片（LSB）的关键。细胞内截短和点突变体证明EphB2催化活性对于LSB形成是必不可少的。这与巢蛋白阳性神经祖细胞中EphB2的表达一致，巢蛋白阳性神经祖细胞从侧脑室"齿状切迹"神经上皮向内侧迁移以填充三级基质并在脑中线附近形成DG。缺乏肝配蛋白-B1的动物再现了受体的损失，并表明该分子作为配体刺激EphB2正向信号传导并指导神经祖细胞迁移到三级基质的背侧隔室中并形成LSB。当EphB2正向信号传导被破坏时，在发育LSB正上方的区域中针对细胞外基质蛋白Reelin的免疫反应性显著降低。总之，这些结果表明ephrin-B1与EphB2相互作用控制齿状突祖细胞迁移到发育中DG的背侧半部分，可能部分是通过影响直接在LSB上方的关键隔室中的Reelin表达。
The dentate gyrus (DG) is one of two areas in the mature brain where stem cells reside to continuously produce new neurons throughout adulthood. While much research is focused on the DG for its roles in adult neurogenesis, little is known regarding how this key region of the brain initially develops to form its distinct architecture. We show here that the murine EphB2 receptor tyrosine kinase is critical for embryonic/postnatal development of a specific region of the DG known as the lateral suprapyramidal blade (LSB). Intracellular truncation and point mutants demonstrate that EphB2 catalytic activity is essential for LSB formation. This is consistent with expression of EphB2 in nestin-positive neural progenitor cells that migrate medially from the lateral ventricle ‘dentate notch’ neuroepithelium to populate the tertiary matrix and form the DG near the midline of the brain. Animals lacking ephrin-B1 recapitulate loss of the receptor and show that this molecule acts as the ligand to stimulate EphB2 forward signaling and direct migration of the neural progenitors into the dorsal compartment of the tertiary matrix and form the LSB. Immunoreactivity against the extracellular matrix protein Reelin in a region directly above the developing LSB is dramatically reduced when EphB2 forward signaling is disrupted. Together, these results indicate ephrin-B1 interacting with EphB2 controls the migration of dentate progenitor cells into the dorsal half of the developing DG, perhaps in part by affecting Reelin expression in a key compartment directly above the LSB.