title: Keratan Sulfate Regulates the Switch from Motor Neuron to Oligodendrocyte Generation During Development of the Mouse Spinal Cord.
abstract: Keratan sulfate (KS) is a sulfated glycosaminoglycan and has been shown to bind to sonic hedgehog (Shh), which act as a morphogen to regulate the embryonic spinal cord development. We found highly sulfated KS was present in the floor plate (including lateral floor plate) and the notochord . This expression colocalized with Shh expression. To understand the roles of KS, we analyzed the embryonic spinal cord of GlcNAc6ST-1, KS chain synthesizing enzyme, knock-out (KO) mice. At E12.5, the pMN domain, whose formation is controlled by Shh signaling, became shifted ventrally in GlcNAc6ST-1 KO mice. In addition, the expression patterns of Patched1 and Gli1, two Shh signaling reporter genes, differed between wild type (WT) and GlcNAc6ST-1 KO mice at E12.5. Next, we focused on cell types generated from the pMN domain; namely, motor neurons and subsequently oligodendrocytes. The number of PDGFRα(+) [a marker for oligodendrocyte precursor cells (OPCs)] cells was low in the E12.5 mutant spinal cord, while motor neuron production was increased. Thus the switch from motor neuron generation to OPC generation was delayed in the pMN domain. Furthermore, we investigated the cause for this delayed switch in the pMN domain. The number of Olig2, Nkx2.2 double-positive cells was less in GlcNAc6ST-1 KO mice than in WT mice. In contrast, the number of Olig2, Neurogenin2 (Ngn2) double-positive cells related to the motor neuron specification was significantly greater in the KO mice. These results indicate that KS is important for the late phase Shh signaling and contributes to motor neuron to OPC generation switch.
authors: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.
authors: Hirokazu
authors: H
authors: Hashimoto
authors: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.
authors: Yugo
authors: Y
authors: Ishino
authors: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.|Department of Physiological Sciences, School of Life Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, 240-0193, Japan.
authors: Wen
authors: W
authors: Jiang
authors: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.|Department of Physiological Sciences, School of Life Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, 240-0193, Japan.
authors: Takeshi
authors: T
authors: Yoshimura
authors: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
authors: Yoshiko
authors: Y
authors: Takeda-Uchimura
authors: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
authors: Kenji
authors: K
authors: Uchimura
authors: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
authors: Kenji
authors: K
authors: Kadomatsu
authors: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan. ikenaka@nips.ac.jp.|Department of Physiological Sciences, School of Life Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, 240-0193, Japan. ikenaka@nips.ac.jp.
authors: Kazuhiro
authors: K
authors: Ikenaka
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D000090322:Homeobox Protein Nkx-2.2; D007632:Keratan Sulfate / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000090322:Homeobox Protein Nkx-2.2; C000715627:Nkx2-2 protein, mouse; D014157:Transcription Factors; D007632:Keratan Sulfate; D000117:Acetylglucosamine
keywords: Keratan sulfate; Motor neuron; Oligodendrocyte; Sonic hedgehog signaling; Spinal cord