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Extracellular matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte
L E Lillien1, M Sendtner, M C Raff
1Biology Department, University College London, United Kingdom.
The Journal of Cell Biology
|August 1, 1990
Summary
Extracellular matrix molecules and ciliary neurotrophic factor (CNTF) together induce stable type-2 astrocyte differentiation from O-2A progenitor cells. ECM molecules also inhibit oligodendrocyte differentiation, mimicking non-glial cell signals in the optic nerve.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- O-2A progenitor cells differentiate into oligodendrocytes and type-2 astrocytes.
- Oligodendrocyte differentiation is constitutive, while type-2 astrocyte differentiation requires extracellular signals like CNTF.
- CNTF alone is insufficient for stable type-2 astrocyte differentiation.
Purpose of the Study:
- To investigate the role of extracellular matrix (ECM) molecules in O-2A progenitor cell differentiation.
- To identify factors cooperating with CNTF for type-2 astrocyte differentiation.
- To elucidate the mechanisms regulating oligodendrocyte and type-2 astrocyte development.
Main Methods:
- Serum-free cell cultures of O-2A progenitor cells.
- Treatment with CNTF, ECM-associated molecules, and basic fibroblast growth factor (bFGF).
- Analysis of oligodendrocyte and type-2 astrocyte differentiation markers.
Main Results:
- ECM molecules cooperate with CNTF to induce stable type-2 astrocyte differentiation, mimicking fetal calf serum (FCS) effects.
- Both ECM molecules and CNTF directly induce premature type-2 astrocyte differentiation in O-2A progenitors.
- ECM molecules inhibit oligodendrocyte differentiation, an effect mimicked by bFGF, but not type-2 astrocyte differentiation.
- ECM-associated molecules responsible for these effects are produced by non-glial cells and are present in the developing optic nerve.
Conclusions:
- A combination of ECM molecules and CNTF is necessary for stable type-2 astrocyte differentiation.
- ECM molecules play a dual role in regulating O-2A progenitor cell fate by promoting astrocyte differentiation and inhibiting oligodendrocyte differentiation.
- These findings suggest a model where non-glial cell-derived ECM molecules interact with CNTF to guide glial cell development in the central nervous system.