22nd Biennial Meeting of the International Society for Developmental Neuroscience
Development of circuits, functions and disorders in the nervous system
タイトル；Area-specific laminar organization is regulated by thalamocortical axons through axon-derived NRN1 and VGF in developing neocortex.
発表者；佐藤 晴香 氏
（熊本大学 発生医学研究所 脳発生分野）
The laminar structures of mammalian neocortex become distinct among areas at later developmental stage. For instance, in the mouse cortex, layer 4 shows relatively uniform distribution throughout the neocortex at birth, but it much thickens in the primary sensory areas compared to other areas after one week. The primary sensory areas receive a dense axonal innervation from the thalamus targeting layer 4 during this period, raising a possibility that the thalamocortical axons (TCAs) extrinsically regulate the cortical laminar organization to establish its area-specificity.
To verify this hypothesis, we acutely ablated thalamic neurons using toxin receptor-mediated cell ablation system in vivo. TCAs were almost completely lost in the primary somatosensory area (S1) during postnatal stage. As a result, the number of layer 4 neurons was significantly reduced, leading to unclear areal distinction in laminar organization in the mutant mice. In contrast, layer 2/3 and 5 were not markedly affected. To reveal the underlying molecular mechanism, we focused on secretory proteins, Neuritin-1 (NRN1) and VGF, which are expressed in the thalamus and emanating from TCAs (Sato et al., 2012). Forced expression of these proteins in S1 layer 4 of mutant mice restored the number of layer 4 neurons in the absence of TCAs. Furthermore, Vgf-deficient mice showed poorly developed layer 4 in the primary sensory areas.
These results indicate that TCAs are required for the development of area-specific laminar organization by regulating the number of layer 4 neurons through the axon-derived secretory proteins.
Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons. Haruka Sato, Yuma Fukutani, Yuji Yamamoto, Eiichi Tatara, Makoto Takemoto, Kenji Shimamura, Nobuhiko Yamamoto. J Neurosci. 32(44):15388-402. 2012.