The role of CD47 in cerebellar granule cell development and medulloblastoma cell proliferation

  • 謝 崇斌

Student thesis: Doctoral Thesis

Abstract

CD47 is an immunoglobulin-like membrane protein that is known to be involved in neuronal differentiation However roles of CD47 in cerebellar development and relevant diseases remain poorly understood At the first part of this study we identify roles of CD47 in cerebellar granule cell development and related behaviors Firstly in situ hybridization was used to determine distribution of CD47 mRNA in the mouse brain during development CD47 mRNA was robustly expressed in the developing cerebellum especially in cerebellar granule cells CD47 protein was mainly expressed in the inner layer of the external granule layer (EGL) molecular layer and internal granule layer (IGL) where granule cells become postmitotic start radial migration and differentiate into mature granule cells respectively By using CD47 knockout mice increased proliferation impaired migration and decreased neurite arborization including reduced number of branches in axonal collaterals and dendrites were found in cerebellar granule cells Meanwhile the length of the fissure between Lobules VI and VII was decreased in CD47 knockout mice In addition CD47 knockout mice exhibited dysfunction in behaviors including increased social interaction at P21 and depressive-like behaviors at 10 wk after birth At the second part of this study we characterized roles of CD47 in proliferation of medulloblastoma cells In human medulloblastoma Daoy cells knockdown of CD47 increased cell proliferation On the contrary overexpression and activation of CD47 significantly inhibited cell proliferation Moreover CD47 activation significantly reduced the expression level of oncogene c-Myc mRNA and protein and the inhibition be reversed by the MAPK inhibitor In addition anti-CD47 antibody significantly increased the proliferation in medulloblastoma cell lines Daoy and VGH-MED but decreased cell number in other neuroblastoma cells such as IMR32 and SK-N-SH cells In summary this study demonstrated that CD47 regulates cerebellar granule cell development including proliferation migration and neurite differentiation CD47 knockout mice exhibit abnormalities in cerebellar structures and atypical behaviors CD47 inhibits proliferation of medulloblastoma cells via MAPK activation and c-Myc downregulation and anti-CD47 antibody treatment increases proliferation of medulloblastoma Our study not only provides roles of CD47 in cerebellar granule cell development and cerebellum relevant behaviors but also highlight the risk of the application of anti-CD47 antibody on the therapy of cerebellar tumors
Date of Award2015 Jan 30
Original languageEnglish
SupervisorA-Min Huang (Supervisor)

Cite this

The role of CD47 in cerebellar granule cell development and medulloblastoma cell proliferation
崇斌, 謝. (Author). 2015 Jan 30

Student thesis: Doctoral Thesis