Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules.
During central nervous system (CNS) development, glial precursors proliferate in subventricular zones and then migrate throughout the CNS to adopt their final destinations and differentiate into various types of mature glial cells. Although several growth factors promoting the proliferation and/or differentiation of glial precursors have been identified, very little is known about the nature of signals that guide glial cell migration in the CNS. Therefore, we have investigated whether polypeptide growth factors and/or extracellular matrix molecules may mediate the migration of two major glial cell types, type 1 astrocytes and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells. We show that, in a microchemotaxis chamber assay, type 1 astrocytes move toward laminin and complement-derived C5a. Astrocyte migration toward laminin is inhibited by a laminin-specific pentapeptide, YIGSR-NH2. In contrast, O-2A progenitors migrate toward platelet-derived growth factor (PDGF), which also functions as a mitogen for these cells. Using a new method to simultaneously assay migration and DNA synthesis, we also demonstrate that O-2A progenitors can migrate toward PDGF even when DNA replication is inhibited with an antimitotic agent. Thus, migration of different types of glial cells can be induced in vitro by specific signaling molecules, which are present in the developing brain and may stimulate migration of glial cells prior to CNS myelination.
Armstrong
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RC
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.
Harvath
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Dubois-Dalcq
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D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis; D015936:Complement C5a / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
D002630:Chemotactic Factors; D005353:Fibronectins; D006133:Growth Substances; D007797:Laminin; D015936:Complement C5a