Mimicking the neurotrophic factor profile of embryonic spinal cord controls the differentiation potential of spinal progenitors into neuronal cells

Masaya Nakamura, Osahiko Tsuji, Barbara S. Bregman, Yoshiaki Toyama, Hideyuki Okano

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Recent studies have indicated that the choice of lineage of neural progenitor cells is determined, at least in part, by environmental factors, such as neurotrophic factors. Despite extensive studies using exogenous neurotrophic factors, the effect of endogenous neurotrophic factors on the differentiation of progenitor cells remains obscure. Here we show that embryonic spinal cord derived-progenitor cells express both ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) mRNA before differentiation. BDNF gene expression significantly decreases with their differentiation into the specific lineage, whereas CNTF gene expression significantly increases. The temporal pattern of neurotrophic factor gene expression in progenitor cells is similar to that of the spinal cord during postnatal development. Approximately 50% of spinal progenitor cells differentiated into astrocytes. To determine the effect of endogenous CNTF on their differentiation, we neutralized endogenous CNTF by administration of its polyclonal antibody. Neutralization of endogenous CNTF inhibited the differentiation of progenitor cells into astrocytes, but did not affect the numbers of neurons or oligodendrocytes. Furthermore, to mimic the profile of neurotrophic factors in the spinal cord during embryonic development, we applied BDNF or neurotrophin (NT)-3 exogenously in combination with the anti-CNTF antibody. The exogenous application of BDNF or NT-3 promoted the differentiation of these cells into neurons or oligodendrocytes, respectively. These findings suggest that endogenous CNTF and exogenous BDNF and NT-3 play roles in the differentiation of embryonic spinal cord derived progenitor cells into astrocytes, neurons and oligodendrocytes, respectively.

Original languageEnglish
Article numbere20717
JournalPLoS One
Volume6
Issue number6
DOIs
Publication statusPublished - 2011

Fingerprint

Ciliary Neurotrophic Factor
neurotrophins
Nerve Growth Factors
spinal cord
Spinal Cord
Brain-Derived Neurotrophic Factor
Stem Cells
neurons
Neurotrophin 3
Oligodendroglia
Gene expression
Astrocytes
Neurons
stem cells
Gene Expression
astrocytes
Antibodies
brain
Embryonic Development
Cell Differentiation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mimicking the neurotrophic factor profile of embryonic spinal cord controls the differentiation potential of spinal progenitors into neuronal cells. / Nakamura, Masaya; Tsuji, Osahiko; Bregman, Barbara S.; Toyama, Yoshiaki; Okano, Hideyuki.

In: PLoS One, Vol. 6, No. 6, e20717, 2011.

Research output: Contribution to journalArticle

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