Fate determination of neural crest cells by NOTCH-mediated lateral inhibition and asymmetrical cell division during gangliogenesis.
Avian trunk neural crest cells give rise to a variety of cell types including neurons and satellite glial cells in peripheral ganglia. It is widely assumed that crest cell fate is regulated by environmental cues from surrounding embryonic tissues. However, it is not clear how such environmental cues could cause both neurons and glial cells to differentiate from crest-derived precursors in the same ganglionic locations. To elucidate this issue, we have examined expression and function of components of the NOTCH signaling pathway in early crest cells and in avian dorsal root ganglia. We have found that Delta1, which encodes a NOTCH ligand, is expressed in early crest-derived neuronal cells, and that NOTCH1 activation in crest cells prevents neuronal differentiation and permits glial differentiation in vitro. We also found that NUMB, a NOTCH antagonist, is asymmetrically segregated when some undifferentiated crest-derived cells in nascent dorsal root ganglia undergo mitosis. We conclude that neuron-glia fate determination of crest cells is regulated, at least in part, by NOTCH-mediated lateral inhibition among crest-derived cells, and by asymmetric cell division.
Wakamatsu
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Y
Institute of Neuroscience, University of Oregon, Eugene, OR 97403-1254, USA. weston@uoneuro.uoregon.edu
Maynard
T M
TM
Weston
J A
JA
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D003001:Cloning, Molecular; D003370:Coturnix / Q000196:embryology; D029721:Drosophila Proteins; D005724:Ganglia / Q000166:cytology / Q000196:embryology*; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D007605:Juvenile Hormones / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008938:Mitosis; D009432:Neural Crest / Q000196:embryology*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000502:physiology; D051880:Receptors, Notch; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007605:Juvenile Hormones; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein; C060606:numb protein, Drosophila; D001973:Bromodeoxyuridine