Nural Hikmet F, Mastick Grant S
Biochemistry Graduate Program, and Biology Department, University of Nevada, Reno, Nevada 89557, USA.
J Comp Neurol. 2004 Nov 22;479(4):399-409. doi: 10.1002/cne.20317.
We have characterized a system of early neurons that establish the first two major longitudinal tracts in the embryonic mouse forebrain. Axon tracers and antibody labels were used to map the axon projections in the thalamus from embryonic days 9.0-12, revealing several distinct neuron populations that contributed to the first tracts. Each of the early axon populations first grew independently, pioneering a short segment of new tract. However, each axon population soon merged with other axons to form one of only two shared longitudinal tracts, both descending: the tract of the postoptic commissure (TPOC), and, in parallel, the stria medullaris. Thus, the forebrain longitudinal tracts are pioneered by a relay of axons, with distinct axon populations pioneering successive segments of these pathways. The extensive merging of tracts suggests that axon-axon interactions are a major guidance mechanism for longitudinal axons. Several axon populations express tyrosine hydroxylase, identifying the TPOC as a major pathway for forebrain dopaminergic projections. To start a genetic analysis of pioneer axon guidance, we have identified the transcription factor Pax6 as critical for tract formation. In Pax6 mutants, both longitudinal tracts failed to form due to errors by every population of early longitudinal axons. Taken together, these results have identified potentially important interactions between series of pioneer axons and the Pax6 gene as a general regulator of longitudinal tract formation in the forebrain.
我们已经鉴定出一个早期神经元系统，该系统在胚胎小鼠前脑中建立了最初的两条主要纵向神经束。利用轴突示踪剂和抗体标记物来绘制胚胎第9.0至12天丘脑内的轴突投射图，揭示了几个不同的神经元群体，它们共同形成了最初的神经束。每个早期轴突群体最初都是独立生长的，开拓出一小段新的神经束。然而，每个轴突群体很快就与其他轴突合并，形成仅有的两条共同的纵向神经束之一，且都是下行的：视交叉后束（TPOC），与之平行的还有髓纹。因此，前脑纵向神经束是由一系列轴突开拓形成的，不同的轴突群体开拓这些通路的连续节段。神经束的广泛合并表明轴突 - 轴突相互作用是纵向轴突的主要导向机制。几个轴突群体表达酪氨酸羟化酶，这表明TPOC是前脑多巴胺能投射的主要通路。为了启动对先驱轴突导向的遗传学分析，我们已经确定转录因子Pax6对神经束形成至关重要。在Pax6突变体中，由于早期纵向轴突的每个群体都出现错误，两条纵向神经束均未能形成。综上所述，这些结果确定了一系列先驱轴突与Pax6基因之间潜在的重要相互作用，Pax6基因是前脑纵向神经束形成的一般调节因子。
