Regulation of Dendritic Branching and Spine Maturation by Semaphorin3A-Fyn Signaling

• DOI: 10.1523/jneurosci.5453-05.2006
• Publication Date: 2006-03-15T18:18:10Z
• Authors: Asa Morita; Naoya Yamashita; Yukio Sasaki; Yutaka Uchida; Oumi Nakajima; Fumio Nakamura; Takeshi Yagi; Masahiko Taniguchi; Hiroshi Usui; Ritsuko Katoh-Semba; Kohtaro Takei; Yoshio Goshima
• Keywords: Cerebral Cortex; Mice, Knockout; Neurons; 0301 basic medicine; Mice, Inbred ICR; Genotype; Intracellular Signaling Peptides and Proteins; Presynaptic Terminals; Membrane Proteins; Dendrites; Proto-Oncogene Proteins c-fyn; Actins; Mice; 03 medical and health sciences; Morphogenesis; Animals; Pyrazoles; Phosphorylation; Disks Large Homolog 4 Protein; Guanylate Kinases; Protein Processing, Post-Translational; Cells, Cultured

A member of semaphorin family, semaphorin3A (Sema3A), acts as a chemorepellent or chemoattractant on a wide variety of axons and dendrites in the development of the nervous systems. We here show that Sema3A induces clustering of both postsynaptic density-95 (PSD-95) and presynaptic synapsin I in cultured cortical neurons without changing the density of spines or filopodia. Neuropilin-1 (NRP-1), a receptor for Sema3A, is present on both axons and dendrites. When the cultured neurons are exposed to Sema3A, the cluster size of PSD-95 is markedly enhanced, and an extensive colocalization of PSD-95 and NRP-1 or actin-rich protrusion is seen. The effects of Sema3A on spine morphology are blocked by PP2, an Src type tyrosine kinase inhibitor, but not by the PP3, the inactive-related compound. In the cultured cortical neurons fromfyn−/−mice, dendrites bear few spines, and Sema3A does not induce PSD-95 cluster formation on the dendrites. Sema3A and its receptor genes are highly expressed during the synaptogenic period of postnatal days 10 and 15. The cortical neurons in layer V, but not layer III, show a lowered density of synaptic bouton-like structure on dendrites insema3A- andfyn-deficient mice. The neurons of the double-heterozygous mice show the lowered spine density, whereas those of single heterozygous mice show similar levels of the spine density as the wild type. These findings suggest that the Sema3A signaling pathway plays an important role in the regulation of dendritic spine maturation in the cerebral cortex neurons.