A pericellular hyaluronan matrix is required for the morphological maturation of cortical neurons

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 10; p. 129679
• Main Authors: Takechi, Mina, Oshima, Kenzi, Nadano, Daita, Kitagawa, Hiroshi, Matsuda, Tsukasa, Miyata, Shinji
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2020
• Subjects: adults; Animals; Cells, Cultured; cerebral cortex; Cerebral Cortex - cytology; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Cerebral cortical development; extracellular matrix; Extracellular Matrix - metabolism; Hyaluronan; Hyaluronan synthase; hyaluronic acid; Hyaluronic Acid - metabolism; in vitro culture; Mice; Mice, Inbred ICR; Neurite outgrowth; neurites; Neurogenesis; Neurons - cytology; Neurons - metabolism; neuroplasticity; postnatal development; solubility; synapse; Hyaluronan; Cerebral cortical development; Hyaluronan synthase; Neurite outgrowth
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2020.129679

Hyaluronan (HA) is a major component of the extracellular matrix (ECM) and is involved in many cellular functions. In the adult brain, HA forms macromolecular aggregates around synapses and plays important roles in neural plasticity. In contrast to the well-characterized function of HA in the adult brain, its roles in the developing brain remain largely unknown. Biochemical and histochemical analyses were performed to analyze the amount, solubility, and localization of HA in the developing mouse brain. By combining in utero labeling, cell isolation, and in vitro cultures, we examined the expression of hyaluronan synthase (HAS) and morphological maturation of cortical neurons. The amount of HA increased during perinatal development and decreased in the adult. HA existed as a soluble form in the early stages; however, its solubility markedly decreased during postnatal development. HA localized in cell-sparse regions in the embryonic stages, but was broadly distributed during the postnatal development of the cerebral cortex. Developing cortical neurons expressed both Has2 and Has3, but not Has1, suggesting the autonomous production of HA by neurons themselves. HA formed a pericellular matrix around the cell bodies and neurites of developing cortical neurons, and the inhibition of HA synthesis reduced neurite outgrowth. The formation of the pericellular HA matrix is essential for the proper morphological maturation of developing neurons. This study provides new insights into the roles of hyaluronan in the brain. development. •Hyaluronan increases during the perinatal period and decreases in the postnatal period of the brain development.•The solubility of hyaluronan markedly decreases during postnatal development.•Developing cortical neurons autonomously produce hyaluronan.•Hyaluronan forms a pericellular matrix around the cell bodies and neurites of neurons.•Inhibition of hyaluronan synthesis reduces neurite outgrowth of developing cortical neurons.