Department of Neurosciences, College of Medicine, University of Toledo, Ohio, USA.
Anat Rec (Hoboken). 2012 Jan;295(1):105-12. doi: 10.1002/ar.21485. Epub 2011 Dec 7.
Several Eph receptors, prominently EphA4 and EphA7, and their corresponding ligands are known to influence neocortical development, including topographic sorting of thalamocortical axons within primary somatosensory cortex (SI). This study investigated postnatal expression of a ligand that can bind to these receptors, ephrin-A2. Quantitative methods revealed that expression of ephrin-A2 mRNA in SI reached maximum levels on postnatal day (P) 4 and dropped thereafter to background by P18. Ephrin-A2 mRNA expression assessed by in situ hybridization qualitatively revealed a similar time course and localized the expression pattern primarily in two broad laminae in SI, comprising the supragranular and infragranular layers, and with additional expression in the subplate. This expression pattern was investigated in greater detail using immunohistochemistry for ephrin-A2 protein. Immunoreactivity generally showed the same laminar distribution as seen with in situ hybridization, except that it persisted longer, lasting to approximately P14. Expression in the cortical plate was low or absent within presumptive layer IV, and it remained so as cortical lamination progressed. Double-labeling immunohistochemistry with confocal microscopy revealed that cortical neurons were the principal elements expressing ephrin-A2 protein. These findings are consistent with possible involvement of ephrin-A2, in concert with one or more Eph receptors, in influencing arbor development of thalamocortical axons at cortical layer IV boundaries.
几种 Eph 受体,尤其是 EphA4 和 EphA7,以及它们相应的配体,已知会影响新皮层的发育,包括丘脑皮质轴突在初级体感皮层 (SI) 内的拓扑排序。本研究调查了一种能够与这些受体结合的配体 Ephrin-A2 的产后表达。定量方法显示,Ephrin-A2 mRNA 在 SI 中的表达在出生后第 4 天达到最高水平,此后至第 18 天降至背景水平。通过原位杂交定性评估的 Ephrin-A2 mRNA 表达揭示了相似的时间过程,并将表达模式主要定位在 SI 的两个宽阔层中,包括颗粒上层和颗粒下层,并在基板中有额外的表达。使用 Ephrin-A2 蛋白的免疫组织化学更详细地研究了这种表达模式。免疫反应性通常表现出与原位杂交相同的层分布,只是它持续的时间更长,持续到大约 P14。在皮质板中,假定的第四层内的表达较低或不存在,并且随着皮质分层的进展,它仍然如此。使用共聚焦显微镜的双标记免疫组织化学显示,皮质神经元是表达 Ephrin-A2 蛋白的主要元素。这些发现与 Ephrin-A2 可能与一个或多个 Eph 受体一起参与影响丘脑皮质轴突在皮质 IV 层边界处的树突发育相一致。