Cell Lineage Analysis of the Forebrain Structures

本研究项目的目的是阐明神经元的起源，这些神经元构成神经上皮层上的某些脑结构。作为实现这一目标的第一步，我们专注于大脑的丘脑区域，该区域由称为脑核的神经元簇组成，以解决这些神经元如何被指定以及这些核结构如何在发育过程中形成。我们已经发现，一些转录因子表达在特定的脑核团在丘脑。他们的表达的发病被发现在不同的人群中的有丝分裂后的细胞在早期的地幔层的丘脑的雏形，这是受调节的差异活动的Sonic刺猬的方式与其作为一个morphogen的行动。这种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体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，并取决于周围环境。这些结果表明：（1）在发育早期部分由诱导机制产生的相对简单的模式导致在丘脑原基内的特定位置产生不同的神经元群体，（2）这些不同的群体然后经历它们固有的特定迁移，这可能最终产生更复杂的模式，例如发育的丘脑中的核组织。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.