細胞認識・接着分子群による神経回路形成の制御―嗅覚神経系をモデルシステムとして

Neural circuit formation by cell recognition/adhesion molecules with special reference to the olfactory system

神経回路形成の様々なステップで細胞間の認識・接着を司る分子群が，重要な役割を果たしている。特に軸索伸長，ガイダンス，樹状突起形態形成，シナプス形成などの過程において，多種多様な細胞認識分子が時空間的に厳密に制御されながら発現し，機能することによって，複雑であるが秩序だった神経回路網が構築される。本総説では嗅覚神経系に焦点を絞り，これら分子群の役割について解説する。嗅上皮から嗅球へ至る一次嗅覚経路においては，匂い分子構造を基本とした匂い情報のコーティング様式（匂い地図）と，様々な細胞認識分子群の発現局在パターン（CAMマップ）が密に関連している。また嗅球から嗅皮質へと至る二次嗅覚経路においては，発達期の僧帽細胞軸索束（嗅索）中に，細胞認識分子群の発現によって規定される層構造が存在することが新たに見出された。嗅覚系は神経回路構築と感覚情報コーディングの関連が明確な神経システムであり，細胞認識・接着分子群の機能を研究するために適したモデルシステムである。

Cell recognition/adhesion molecule play crucial roles in various steps of neural development, including the axonal outgrowth and guidance, dendritic morphogenesis, and synapse formation. A variety of cell recognition/adhesion molecules are tightly regulated for their expression in spatial and temporal manners and achieve their functions for establishment of complex but highly ordered neural circuitry. In this review, I focus on the olfactory system, summarize recent topics, and discuss possible roles of cell recognition/adhesion molecules.

　In the primary olfactory pathway（from the olfactory epithelium to the olfactory bulb）, the olfactory sensory neurons expressing a given odorant receptor gene converge axons onto a few topographically fixed glomeruli to make up“odorant receptor map or odor map”on the surface of the olfactory bulb. This map is closely correlated with the expression map of cell recognition/adhesion molecules at the axonal termini of the olfactory sensory neurons（CAM map）. Several important players such as OCAM, Neuropilin/Semaphorin, and Eph/Ephrin have identified that are likely to mediate the zone-to-zone projection and the precise glomerular targeting of olfactory axons.

　In contrast, little has been known on molecular and cellular mechanisms underlying formation of the secondary olfactory pathway（from the olfactory bulb to the olfactory cortex）. However, we recently found the laminar organization of the developing lateral olfactory tract that are defined by differential expression of cell recognition/adhesion molecules, suggesting that the developing mitral cell axons are not homogeneous.

　The olfactory system is a good model to study the roles of cell recognition/adhesion molecules, related to the neural circuit formation and the odor information coding.