Deficits in cerebellar granule cell development and social interactions in CD47 knockout mice

Chung Pin Hsieh, Wen Teng Chang, Yi Chao Lee, A. Min Huang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

CD47 is involved in neurite differentiation in cultured neurons, but the function of CD47 in brain development is largely unknown. We determined that CD47 mRNA was robustly expressed in the developing cerebellum, especially in 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 individually become postmitotic and migrate, leading to neurite fasciculation. At postnatal day 8 (P8), CD47 knockout mice exhibited an increased number of proliferating granule cells in the EGL, whereas the CD47 agonist peptide 4N1K increased the number of postmitotic cells in primary granule cells. Knocking out the CD47 gene and anti-CD47 antibody impaired the radial migration of granule cells from the EGL to the IGL individually in mice and slice cultures. In primary granule cells, knocking out CD47 reduced the number of axonal collaterals and dendritic branches; by contrast, overexpressing CD47 or 4N1K treatment increased the axonal length and numbers of axonal collaterals and dendritic branches. Furthermore, the length of the fissure between Lobules VI and VII was decreased in CD47 knockout mice at P21 and at 14 wk after birth. Lastly, CD47 knockout mice exhibited increased social interaction at P21 and depressive-like behaviors at 10 wk after birth. Our study revealed that the cell adhesion molecule CD47 participates in multiple phases of granule cell development, including proliferation, migration, and neurite differentiation implying that aberrations of CD47 are risk factors that cause abnormalities in cerebellar development and atypical behaviors.

Original languageEnglish
Pages (from-to)463-484
Number of pages22
JournalDevelopmental Neurobiology
Volume75
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Interpersonal Relations
Knockout Mice
Cell Communication
Neurites
Parturition
Cell Adhesion Molecules
Cerebellum
Cell Movement
Anti-Idiotypic Antibodies
Cell Count
Neurons
Messenger RNA
Brain
Genes
Proteins

Keywords

  • CD47
  • Cerebellar development
  • Granule cells
  • Proliferation
  • Social interaction

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Deficits in cerebellar granule cell development and social interactions in CD47 knockout mice. / Hsieh, Chung Pin; Chang, Wen Teng; Lee, Yi Chao; Huang, A. Min.

In: Developmental Neurobiology, Vol. 75, No. 5, 01.05.2015, p. 463-484.

Research output: Contribution to journalArticle

Hsieh, Chung Pin ; Chang, Wen Teng ; Lee, Yi Chao ; Huang, A. Min. / Deficits in cerebellar granule cell development and social interactions in CD47 knockout mice. In: Developmental Neurobiology. 2015 ; Vol. 75, No. 5. pp. 463-484.
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