Department of Physiology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Radioisotope Center, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
PLoS One. 2019 Aug 20;14(8):e0221440. doi: 10.1371/journal.pone.0221440. eCollection 2019.
The corpus callosum (CC) is the biggest commissure that links cerebral hemispheres. Guidepost structures develop in the cortical midline during CC development and express axon guidance molecules that instruct neurons regarding the proper direction of axonal elongation toward and across the cortical midline. Neuropilin-1 (Npn1), a high affinity receptor for class 3 semaphorins (Sema3s) localized on cingulate pioneering axons, plays a crucial role in axon guidance to the midline through interactions with Sema3s. However, it remains unclear which type of Plexin is a component of Sema3 holoreceptors with Npn1 during the guidance of cingulate pioneering axons. To address the role of PlexinA1 in CC development, we examined with immunohistochemistry the localization of PlexinA1, Npn1, and Sema3s using embryonic brains from wild-type (WT) and PlexinA1-deficient (PlexinA1 knock-out (KO)) mice with a BALB/cAJ background. The immunohistochemistry confirmed the expression of PlexinA1 in callosal axons derived from the cingulate and neocortex of the WT mice on embryonic day 17.5 (E17.5) but not in the PlexinA1 KO mice. To examine the role of PlexinA1 in the navigation of callosal axons, the extension of callosal axons toward and across the midline was traced in brains of WT and PlexinA1 KO mice at E17.5. As a result, callosal axons in the PlexinA1 KO brains had a significantly lower incidence of midline crossing at E17.5 compared with the WT brains. To further examine the role of PlexinA1 in CC development, the CC phenotype was examined in PlexinA1 KO mice at postnatal day 0.5 (P0.5). Most of the PlexinA1 KO mice at P0.5 showed agenesis of the CC. These results indicate the crucial involvement of PlexinA1 in the midline crossing of callosal axons during CC development in BALB/cAJ mice.
胼胝体（CC）是连接大脑半球的最大连合。在 CC 发育过程中，皮质中线处会发育出引导结构，并表达指导神经元轴突向皮质中线正确伸长方向的轴突导向分子。神经纤毛蛋白-1（Npn1）是一种位于扣带回先驱轴突上的高亲和力类 3 神经丝氨酸蛋白（Sema3s）受体，在与 Sema3s 的相互作用下，在轴突向中线的导向中发挥关键作用。然而，在扣带回先驱轴突的导向中，哪种类型的 Plexin 是 Npn1 与 Sema3 全受体的组成部分仍不清楚。为了研究 PlexinA1 在 CC 发育中的作用，我们使用来自 BALB/cAJ 背景的野生型（WT）和 PlexinA1 缺陷型（PlexinA1 敲除（KO））小鼠的胚胎脑，通过免疫组织化学方法检查了 PlexinA1、Npn1 和 Sema3s 的定位。免疫组织化学证实，WT 小鼠 E17.5 时扣带回和新皮质来源的 CC 轴突表达 PlexinA1，但 PlexinA1 KO 小鼠则不表达。为了研究 PlexinA1 在 CC 轴突导航中的作用，我们在 E17.5 时追踪 WT 和 PlexinA1 KO 小鼠大脑中 CC 轴突向中线的延伸和穿过中线的情况。结果表明，与 WT 脑相比，PlexinA1 KO 脑的 CC 轴突中线穿越率显著降低。为了进一步研究 PlexinA1 在 CC 发育中的作用，我们在 P0.5 时检查了 PlexinA1 KO 小鼠的 CC 表型。大多数 P0.5 时的 PlexinA1 KO 小鼠 CC 发育不全。这些结果表明，在 BALB/cAJ 小鼠中，PlexinA1 对 CC 发育过程中 CC 轴突的中线穿越至关重要。
