Ectopic Reelin Induces Neuronal Aggregation with a Normal Birthdate-Dependent "Inside-Out" Alignment in the Developing Neocortex
Ectopic Reelin Induces Neuronal Aggregation with a Normal Birthdate-Dependent "Inside-Out" Alignment in the Developing Neocortex
复制标题
DOI：
10.1523/jneurosci.0486-10.2010
复制
发表时间：
2010-08-18
影响因子：
5.3
通讯作者：
Nakajima, Kazunori
中科院分区：
文献类型：
--
作者：
Kubo, Ken-ichiro;Honda, Takao;Nakajima, Kazunori
发育中的哺乳动物新皮质中的神经元以“内向外”的方式形成皮质板（CP）；也就是说，较早出生的神经元形成较深的神经元层，而较晚出生的神经元越过现有的神经元层，形成较浅的神经元层。Reelin是一种由Cajal-Retzius神经元在边缘区（MZ）分泌的糖蛋白，对于这种“由内而外”的分层至关重要，因为在Reelin缺乏的小鼠reeler （Relnrl）中，这些层是颠倒的。尽管自发现reelin以来已经过去了十多年，但reelin对个体迁移神经元的生物学作用仍不清楚。此外，尽管Reelin在卷轴皮层中缺失MZ，但Reelin是否直接调节细胞体稀疏MZ的发育尚不清楚。为了解决这些问题，我们在发育中的小鼠皮质中异位表达了Reelin，结果表明，Reelin导致迁移神经元的主要过程在富含Reelin的区域聚集，从而诱导其细胞体在Reelin周围形成细胞聚集体。有趣的是，异位的富含reelin的区域变得细胞体稀疏，树突丰富，类似于MZ，并且晚出生的神经元迁移到聚集体内的中央富含reelin的区域，导致出生日期依赖的“内向外”排列甚至是异位的。研究发现，Reelin受体和细胞内接头蛋白Dab1是形成聚集体所必需的。上述研究结果表明，Reelin信号能够诱导树突丰富、细胞体稀疏的MZ的形成，并独立于MZ附近的其他因素/结构，诱导神经元的“内向外”排列。
Neurons in the developing mammalian neocortex form the cortical plate (CP) in an "inside-out" manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal-Retzius neurons in the marginal zone (MZ), is crucial for this "inside-out" layering, because the layers are inverted in the Reelin-deficient mouse, reeler (Relnrl). Even though more than a decade has passed since the discovery of reelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in the reeler cortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent "inside-out" alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent "inside-out" alignment of neurons independently of other factors/structures near the MZ.