Hernández-Montiel Hebert L, Meléndez-Herrera Esperanza, Cepeda-Nieto Ana C, Mejía-Viggiano Carmen, Larriva-Sahd Jorge, Guthrie Sarah, Varela-Echavarría Alfredo
Institute for Neurobiology, Universidad Nacional Autónoma de México, Campus UNAM-UAQ Juriquilla, Querétaro, Mexico.
Dev Biol. 2003 Mar 1;255(1):99-112. doi: 10.1016/s0012-1606(02)00033-7.
We have addressed the control of longitudinal axon pathfinding in the developing hindbrain, including the caudal projections of reticular and raphe neurons. To test potential sources of guidance signals, we assessed axon outgrowth from embryonic rat hindbrain explants cultured in collagen gels at a distance from explants of midbrain-hindbrain boundary (isthmus), caudal hindbrain, or cervical spinal cord. Our results showed that the isthmus inhibited caudally directed axon outgrowth by 80% relative to controls, whereas rostrally directed axon outgrowth was unaffected. Moreover, caudal hindbrain or cervical spinal cord explants did not inhibit caudal axons. Immunohistochemistry for reticular and raphe neuronal markers indicated that the caudal, but not the rostral projections of these neuronal subpopulations were inhibited by isthmic explants. Companion studies in chick embryos showed that, when the hindbrain was surgically separated from the isthmus, caudal reticulospinal axon projections failed to form and that descending pioneer axons of the medial longitudinal fasciculus (MLF) play an important role in the caudal reticulospinal projection. Taken together, these results suggest that diffusible chemorepellent or nonpermissive signals from the isthmus and substrate-anchored signals on the pioneer MLF axons are involved in the caudal direction of reticulospinal projections and might influence other longitudinal axon projections in the brainstem.
我们已经研究了发育中后脑纵向轴突寻路的控制，包括网状和中缝神经元的尾侧投射。为了测试潜在的导向信号来源，我们评估了在胶原凝胶中培养的胚胎大鼠后脑外植体的轴突生长情况，这些外植体与中脑-后脑边界（峡部）、尾侧后脑或颈脊髓的外植体保持一定距离。我们的结果表明，相对于对照组，峡部抑制了80%的尾侧轴突生长，而头侧轴突生长则未受影响。此外，尾侧后脑或颈脊髓外植体并未抑制尾侧轴突。对网状和中缝神经元标志物的免疫组织化学分析表明，峡部外植体抑制了这些神经元亚群的尾侧而非头侧投射。在鸡胚中的相关研究表明，当后脑通过手术与峡部分离时，尾侧网状脊髓轴突投射无法形成，并且内侧纵束（MLF）的下行先驱轴突在尾侧网状脊髓投射中起重要作用。综上所述，这些结果表明，来自峡部的可扩散化学排斥或非许可信号以及先驱MLF轴突上的底物锚定信号参与了网状脊髓投射的尾侧方向，并且可能影响脑干中的其他纵向轴突投射。
