Glial growth factor restricts mammalian neural crest stem cells to a glial fate.
Growth factors and cytokines are thought to influence the development of uncommitted progenitor cell populations, but the issue of how these factors act on individual cells remains controversial. Such factors may act simply as selective mitogens or survival factors for cells that undergo lineage restrictions stochastically. Alternatively, they may instruct or bias multipotent cells to choose one lineage at the expense of others. Here we show that glial growth factor (GGF), previously defined as a Schwann cell mitogen, strongly suppresses neuronal differentiation of rat neural crest stem cells while promoting or allowing glial differentiation. Quantitative clonal analysis suggests that the action of GGF is likely to be instructive rather than selective. Taken together with the expression pattern of GGF, these data suggest a lateral signaling model for the diversification of cell types within developing peripheral ganglia.
Shah
N M
NM
Division of Biology, California Institute of Technology, Pasadena 91125.
Marchionni
M A
MA
Isaacs
I
I
Stroobant
P
P
Anderson
D J
DJ
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002999:Clone Cells; D005576:Colforsin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D017950:Ganglia, Sensory / Q000737:chemistry / Q000196:embryology / Q000378:metabolism; D020904:Glia Maturation Factor; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000032:analysis; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D009432:Neural Crest / Q000737:chemistry / Q000187:drug effects / Q000196:embryology*; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology*; D009479:Neuropeptides / Q000032:analysis; D064531:Peripherins; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D014157:Transcription Factors / Q000032:analysis
D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D005576:Colforsin; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D020904:Glia Maturation Factor; D005904:Glial Fibrillary Acidic Protein; D006131:Growth Inhibitors; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D064531:Peripherins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D014157:Transcription Factors; C499318:Ascl1 protein, rat