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Axonal/Dendritic Growth and Circuit Formation

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Analysis of the Corticospinal Tract Formation in Adult Sulf1;Sulf2 Double Knockout Mice

  • P2-105
  • 岡田 拓也 / Takuya Okada:1 加賀屋 菜々 / Nana Kagaya:1 桝 和子 / Kazuko Keino-Masu:1 桝 正幸 / Masayuki Masu:1 
  • 1:筑波大 医学医療系 分子神経生物 / Dept Mol Neurobiol, Fac Med, Univ of Tsukuba, Ibaraki, Japan 

Heparan sulfate proteoglycans (HSPGs) are highly glycosylated proteins present on the cell surface and in the extracellular matrix. They control cell proliferation, differentiation, migration, axon guidance, and synaptogenesis during neural development. Heparan sulfate (HS) that is covalently attached to the HSPG core proteins exerts these diverse functions by interacting with a wide variety of proteins, including growth factors, morphogens, axon guidance molecules, and their receptors. The specificity and affinity of the ligand interactions, which are determined by sulfation patterns of HS, play a pivotal role in the functional modulation of HSPGs. HS endosulfatases, Sulf1 and Sulf2, modify the sulfation patterns of HS extracellularly, thereby regulating multiple signaling pathways. Previously, we reported that Sulf1/2 double knockout (DKO) mice showed axon guidance defects in the corticospinal tract (CST). Because most of the Sulf1/2 DKO mice died within a day of birth in the C57BL/6 background, we could not examine the postnatal development of the CST, especially whether the pyramidal decussation is formed. In this study, we report that when backcrossed to ICR/CD-1 mice, Sulf1/2 DKO mice survive to adulthood and show the CST defects. When the brain sections of adult Sulf1/2 DKO mice were immunostained with protein kinase C gamma (PKCγ) antibody, a postnatal CST marker, abnormal defasciculated fibers were observed on the lateral surface of the midbrain as seen in the neonatal Sulf1/2 DKO mice in the C57BL/6 background. Most of the abnormal fibers extended dorsally towards the tectum and then returned to the pons, whereas some fibers invaded the superior and inferior colliculi. In the medulla, returned axons were defasciculated and positioned more laterally compared with the controls. At the pyramidal decussation, the majority of the CST fibers failed to turn dorsally and cross the midline, extending in the lateral position of the ipsilateral ventral spinal cord. These data suggest that Sulfs control the CST axon guidance including the formation of the pyramidal decussation.

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