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

Abstract

AbstractRadial neuronal migration is a key neurodevelopmental event for proper cortical laminar organization. Newly born neurons migrate in a complex three-dimensional environment generated by the extracellular matrix (ECM), secreted factors, and neighboring cells. However, the molecular mechanisms by which the ECM controls radial migration remain largely unknown. We herein identified neurocan (NCAN), a risk factor for neuropsychiatric disorders, as a major chondroitin sulfate proteoglycan produced by developing cortical neurons. 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. 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, TNC in the ternary complex promotes neuronal morphological maturation. The present results provide evidence for the cooperative role of neuron- and radial glial cell-derived ECM molecules in cortical development.