GSBS Student Publications

Title

Embryonic precursor cells that express Trk receptors: induction of different cell fates by NGF, BDNF, NT-3, and CNTF

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Cancer Center; Department of Neurology; Department of Biochemistry and Molecular Pharmacology

Date

4-1-1997

Document Type

Article

Medical Subject Headings

Animals; Biological Markers; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Division; Cell Lineage; Cells, Cultured; Choline O-Acetyltransferase; Ciliary Neurotrophic Factor; Corpus Striatum; Epidermal Growth Factor; Extracellular Matrix; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Nerve Growth Factors; Nerve Tissue Proteins; Neurons; Neurotrophin 3; Oligodendroglia; Receptors, Nerve Growth Factor; Recombinant Proteins; Stem Cells; Tyrosine 3-Monooxygenase

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Epidermal growth factor (EGF)-treated neurosphere cultures from embryonal striatum contain multipotential cells capable of neuronal, astrocytic, and oligodendroglial differentiation. In this study, we tested whether these neural precursor cells differentiate in the presence of neurotrophic factors. We first assayed neurosphere cells for expression of neurotrophin receptors. TrkA, TrkB, TrkC, and gp75 were detected by immunofluorescence microscopy in 60-80% of cells. In addition, the ciliary neurotrophic factor receptor alpha was expressed in 50-60% of cells. In the presence of the mitogen, EGF, treatment of stem cells with neurotrophic factors had no apparent effect. Removal of EGF from cells resulted in cessation of cell proliferation and pronounced astrocytic (glial fibrillary acidic protein+) differentiation. Neuronal (neurofilament+) and oligodendroglial (galactocerebroside+) cells appeared in cultures treated with neurotrophic factors. Nerve growth factor (NGF) resulted in bipolar neuronal cells, and brain-derived neurotrophic factor led to multipolar neuronal cells. Treatment with neurotrophin-3 or ciliary neurotrophic factor resulted in bipolar neuronal cells and oligodendrocytes. Neuronal differentiation in the presence of NGF was enhanced by extracellular matrix, and the resulting neuronal cells expressed choline acetyltransferase and, to a lesser degree, tyrosine hydroxylase. These studies demonstrate that neurotrophic factors influence the fates of these multipotential precursor cells. Indeed, the true utility of multipotential precursor cells is the production of different types of cells in different situations. Local cues, such as neurotrophic factors and extracellular matrix, may regulate production of different types of neural cells during development or in response to other stimuli, such as injury.

Rights and Permissions

Citation: Exp Neurol. 1997 Apr;144(2):350-60. Link to article on publisher's site

DOI of Published Version

10.1006/exnr.1997.6434

Related Resources

Link to article in PubMed

Journal Title

Experimental neurology

PubMed ID

9168835