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内容記述 |
A remarkable feature of the mammalian evolution is the expansion of the<br />neocortex and emergence of the specific internal cytoarchitecture, the layer<br />structure. All of the mammalian species share the neocortical layer structure, in<br />which a similar type of neurons are arranged in a particular layer parallel to the<br />brain surface. During the neocortical de-velopment, the neuronal subtypes in the<br />neocortical layers are produced from neural progenitor cells in a stereotyped<br />temporal sequence from deep to upper layers. This stereotyped sequence of<br />neuronal production is attributed to the temporal restriction of the competence<br />of neural progenitors. The progenitors initially possess the multipotency to<br />generate the neuronal subtypes in all neocortical layers, but gradually loose the<br />potency during the development, and eventually become only able to produce the<br />upper layer neurons.<br /> The dorsal region of the telencephalon called the pallium is the<br />non-mamalian homologue of the neocortex, because the same developmentally<br />important genes are commonly expressed in the mammalian neocortex and the<br />non-mammalian pallium. Although the pallium is completely conserved among<br />the vertebrates, the internal structure is variable. For example, the bird, one of<br />the closest relatives of the mammals, possesses the well-developed pallium<br />packed with distinct subtypes of neurons that are arranged in particular<br />domains. Such observations suggest that the common ancestor of the mammals<br />and the birds had already acquired the pallium, and that the pallial structure<br />has been modified in an animal group-specific manner through alterations in the<br />developmental processes. Therefore, a key event contributing to the evolutionary<br />emergence of the neocortical layer structure could be found through comparison<br />of the development between the mammalian neocortex and the non-mammalian<br />pallium.<br /> The chick pallium is a good model to approach the problem, because of the<br />closest phylogenetic position to the mammals as well as the convenience of<br />experimental manipulations. For over a century, it has been argued whether the<br />avian pallium has a comparable neuronal repertory to the mammalian neocortex.<br />Therefore, I first checked expression patterns of marker genes for the<br />mammalian neocortical layers in the chick pallium. This analysis revealed that<br />both the deep (layer V) and upper layer (layer II/III) marker genes were<br />expressed in the chick pallium, suggesting that the chick pallium possesses a<br />neuronal repertory similar to the mammalian neocortex. In addition to the<br />molecular expressions, the axon projections were also found to be partially<br />similar between the chick pallial neurons and the corresponding neuronal<br />subtypes of the mammalian neocortex. In spite of the remarkable conservation<br />in the neuronal repertory, spatial distribution patterns of the deep and upper<br />layer neurons were entirely different from the layer arrangement of the<br />mammalian neocortex; in the chick pallium, the deep and upper layer neurons<br />were not arranged in parallel, but distantly located in the medial and lateral<br />side, respectively.<br /> The development of the deep and upper layer neurons in the chick pallium<br />was investigated in detail. First, the birthdate analysis by BrdU pulse-labeling<br />demonstrated that the deep layer neurons were generated earlier than the<br />upper layer neurons in the chick pallium, suggesting that the temporal sequence<br />of the neuron production is evolutionarily conserved between the mammals and<br />the birds. Second, the fate mapping analysis revealed that the deep and upper<br />layer neurons originated from the distinct neural progenitors on the medial and<br />lateral sides in the chick pallium, respectively. This spatially separate<br />production of the neurons is the critical difference from the mammalian<br />neocortical development, in which the deep and upper layer neurons are<br />uniformly produced across the entire neocortex. Probably related to this<br />difference, I found that the late neurogenesis in the chick pallium<br />predominantly occurs on the lateral side. This spatiotemporally biased neuronal<br />production can explain the selective generation of the late-born upper layer<br />neurons only from the lateral side in the chick pallium. Taken together, the<br />distinct neurogenetic properties between the medial and lateral progenitors<br />appeared to be the key to construct the non-layered domain-like cytoarchiteture<br />in the chick pallium.<br /> How then is the medio-lateral difference of neurogenetic properties is<br />instructed in the chick pallium? I cultured neural progenitor cells from the<br />medial and lateral sides of the chick pallium in a clonal density, and<br />surprisingly found that most of the clones derived from a single progenitor cell<br />contained both deep and upper layer neurons, regardless of its origin. This<br />remarkable observation clearly demonstrated that the neural progenitor cells in<br />the medial and lateral sides of the chick pallium intrinsically possess a similar<br />neurogenic competence, and the neurocompetency is extrinsically regulated by<br />the surrounding tissues according to the spatial positions.<br /> On the basis on the results obtained, I propose the following model for the<br />avian pallial development. The avian neural progenitors are intrinsically<br />equivalent to those of mammals and capable of sequentially generating a full<br />repertory of neuronal subtypes. However, the neurogenesis in the avian pallium<br />is extrinsically regulated by two potential mechanisms. First, the deep layer fate<br />in the early-born neurons on the lateral side is suppressed by environmental<br />factors, and thereby, the lateral neural progenitor cells produce only the upper<br />layer neurons in the later phase of neurogenesis. Second, the medial neural<br />progenitors terminate the neurogenesis precociously before producing the upper<br />layer neurons leading to the preferential generation of deep layer neurons from<br />the medial side.<br /> Lastly, the emergence of the layered neocortex in mammals has been a<br />long-standing mystery in evolutionary biology. The present discovery of the<br />evolutionary conservation in the neural progenitor competence between the<br />mammals and the avian suggests that the common ancestor of the amniotes has<br />already possessed the developmental potential to sequentially produce the<br />multiple neuronal subtypes. During the evolutionary diversification into each<br />lineage of animal groups, alterations in the spatial regulation of the<br />neurogenetic program may have contributed to the emergence of animal<br />group-specific brain structures, such as the layer structure in the mammalian<br />neocortex and the domain structure in the avian pallium. |
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