Assembly of neuron- and radial glial-cell-derived extracellular matrix molecules promotes radial migration of developing cortical neurons

• Published in: eLife Vol. 12
• Main Authors: Mubuchi, Ayumu, Takechi, Mina, Nishio, Shunsuke, Matsuda, Tsukasa, Itoh, Yoshifumi, Sato, Chihiro, Kitajima, Ken, Kitagawa, Hiroshi, Miyata, Shinji
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 21.03.2024; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Antibodies; Biochemistry and Chemical Biology; Cell growth; Cell migration; Cell Movement - physiology; Cerebral cortex; Cerebral Cortex - metabolism; Chondroitin sulfate; Chondroitin Sulfate Proteoglycans - metabolism; cortical development; Ethylenediaminetetraacetic acid; Extracellular matrix; Extracellular Matrix - metabolism; Hyaluronic acid; Labeling; Mice; Neurocan; Neuronal-glial interactions; Neurons; Neurons - physiology; Neuroscience; Polysaccharides; Proteoglycans; radial migration; Scientific equipment and supplies industry; Sulfates; Tenascin; Tenascin C; United States; Japan; Iraq; proteoglycans; mouse; chemical biology; neuroscience; tenascin; biochemistry; radial migration; cortical development; extracellular matrix; hyaluronic acid
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.92342

Radial neuronal migration is a key neurodevelopmental event for proper cortical laminar organization. The multipolar-to-bipolar transition, a critical step in establishing neuronal polarity during radial migration, occurs in the subplate/intermediate zone (SP/IZ), a distinct region of the embryonic cerebral cortex. It has been known that the extracellular matrix (ECM) molecules are enriched in the SP/IZ. However, the molecular constitution and functions of the ECM formed in this region remain poorly understood. Here, we identified neurocan (NCAN) as a major chondroitin sulfate proteoglycan in the mouse SP/IZ. NCAN binds to both radial glial-cell-derived tenascin-C (TNC) and hyaluronan (HA), a large linear polysaccharide, forming a ternary complex of NCAN, TNC, and HA in the SP/IZ. Developing cortical neurons make contact with the ternary complex during migration. The enzymatic or genetic disruption of the ternary complex impairs radial migration by suppressing the multipolar-to-bipolar transition. Furthermore, both TNC and NCAN promoted the morphological maturation of cortical neurons in vitro. The present results provide evidence for the cooperative role of neuron- and radial glial-cell-derived ECM molecules in cortical development.