Lunatic fringe potentiates Notch signaling in the developing brain.
Notch signaling is essential for the self-renewal of mammalian neural progenitor cells. A variety of mechanisms modulate Notch signaling to balance the self-renewal and differentiation of progenitor cells. Fringe is a major Notch regulator and promotes or suppresses Notch signaling, depending on the Notch ligands. In the developing brain, Lunatic fringe (Lfng) is expressed in self-renewing progenitors, but its roles are unknown. In this study, in vivo mosaic analyses using in utero electroporation were developed to investigate the roles of Lfng in neural progenitor cells. We found that Lfng potentiates Notch signaling cell-autonomously. Its depletion did not affect the balance between neuronally committed cells and self-renewing progenitors, however, irrespective of the cell density of Lfng-depleted cells, and caused no obvious defects in brain development. In vivo overexpression experiments with Notch ligands suggest that Lfng strongly augments Notch signaling mediated by Delta-like 1 but not Jagged 1.
Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Tomoaki M
TM
Kato
Ayano
A
Kawaguchi
Yoichi
Y
Kosodo
Hitoshi
H
Niwa
Fumio
F
Matsuzaki
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D019556:COS Cells; D002135:Calcium-Binding Proteins; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch; D016695:Glycosyltransferases; C498392:Lfng protein, mouse