Direct cell-cell interactions control apoptosis and oligodendrocyte marker expression of neuroepithelial cells.
During brain development, the neuroepithelium generates neurons and glial cells. Proliferation and differentiation of neuroepithelial cells are controlled by a complex combination of secreted factors and more intrinsic or local mechanisms, such as lateral inhibition and asymmetric division. To obtain further insights into the signals governing neuroepithelial cell fate, we used the immortomouse to derive conditionally immortalised cell lines from mouse E10 neuroepithelium. We isolated a nestin-positive basic fibroblast growth factor (bFGF)-responsive cell line (SVE10-23) which mostly differentiate into astrocytes when cocultured with primary cortical cells. We found that, by simply lowering the cell density, SVE10-23 cells embarked on oligodendrocytic differentiation as indicated by the strong expression of galactocerebroside C and 2'3'-cyclic nucleotide 3'-phosphodiesterase. Apoptosis accompanied the differentiation, and all cells died within 1 week. We present here evidence that direct interactions between cells are the main mechanism regulating this oligodendrocytic differentiation. We demonstrate that SVE10-23 cells contact or proximity inhibit their differentiation, prevent apoptosis, and promote their proliferation. Similarly, others nestin-positive precursor cell lines and nonimmortalised bFGF-grown E10 cells were found to spontaneously differentiate at low density, thus generalising the idea that neural precursor fate is regulated by direct cell-cell interactions. The SVE10-23 cell line provides a valuable tool with which to study further the molecular components implicated in this mode of regulation.
Hugnot
J P
JP
Institute of Psychiatry, Denmark Hill, London, United Kingdom. hugnot@univ-montp2.fr
Mellodew
K
K
Pilcher
H
H
Uwanogho
D
D
Price
J
J
Sinden
J D
JD
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology; D015415:Biomarkers; D002450:Cell Communication; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D019070:Cell Lineage; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D003260:Contact Inhibition; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005699:Galactosylceramides / Q000096:biosynthesis; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007381:Intermediate Filament Proteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D064231:Nestin; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D005699:Galactosylceramides; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016222:Fibroblast Growth Factor 2; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571338:Cnp protein, mouse