Cell Lineage Analysis of the Forebrain Structures

本研究项目的目的是阐明在神经上皮层上构成某些脑结构的神经元的起源。作为实现这一目标的第一步，我们将重点放在大脑的丘脑区域，该区域由称为脑核的神经元簇组成，以解决这些神经元是如何指定的，以及这些核结构是如何在发育过程中形成的。我们发现一些转录因子在丘脑的特定脑核中表达。它们的表达开始于丘脑基底早期地幔层的有丝分裂后细胞的不同群体，这是由Sonic hedgehog基因的差异活性调控的，其方式与Sonic hedgehog基因作为形态原的作用一致。这些不同的诱导活动是由不同的Gli因子选择性介导的。接下来，我们发现一些神经元群通过高度定型的途径从它们的出生地迁移到特定的细胞核。移植实验表明，这种迁移特性是特定种群所特有的，并且依赖于周围的环境。这些结果表明：(1)在发育早期由诱导机制产生的相对简单的模式导致在丘脑基础的特定位置产生不同的神经元群体；(2)这些不同的群体随后经历固有的特定迁移，最终可能产生更复杂的模式，如发达的丘脑中的核组织。我们认为这些过程可能是形成核结构的基本策略。

The aim of this research project was to elucidate the origin of neurons that constitute certain brain structures upon the sheet of neuroepithelium. As a first step to this end, we have focused on the thalamic region of the brain which consists of clusters of neurons called brain nuclei to address how these neurons are specified and how these nuclear structures are formed during development. We have found that several transcription factors are expressed in the specific brain nuclei in the thalamus. The onset of their expression was found in distinct populations of the postmitotic cells in the early mantle layer of the thalamic rudiment, which was regulated by the differential activities of Sonic hedgehog in a manner consistent with its action as a morphogen. Such distinct inductive activities are mediated selectively by different Gli factors. Next we found that some neuronal populations migrate from their birthplace to the particular nuclei through highly stereotyped pathways. Transplantation experiments revealed that this migratory property is unique to the particular populations, and dependent on the surrounding environment. These results suggested a scenario that (1) the relatively simple pattern created early in development in part by inductive mechanisms leads to generation of distinct neuronal populations at defined locations within the thalamic rudiment, and (2) these distinct populations then undergo specific migration intrinsic to them, which may eventually generate more complicated patterns such as the nucleus organization in the developed thalamus. We think that these processes are likely to be basic strategies for the formation of the nuclear structures.