Sequential signaling through Notch1 and erbB receptors mediates radial glia differentiation.
Radial glia cells both generate neurons and physically guide nascent neurons to their target destination in the cortex, and as such they are essential for CNS development. It has been proposed that in the developing cerebellum, neuronal contact induces radial glia formation, however, the mechanisms involved in this process are not well understood. Here we demonstrate that neuronal induction of radial glia formation is the result of sequential signaling through Notch1 and erbB receptors. First, Notch1 activation by neuronal contact induces the glial expression of the brain lipid binding protein (BLBP) and erbB2 genes. Interestingly, two different signaling pathways mediate these effects of Notch1 on transcription, BLBP expression being dependent on Su(H), whereas erbB2 is regulated by a yet unidentified Notch1 pathway. The subsequent increase in erbB2 receptor expression makes the glia more responsive to neuronal NRG, which then induces the morphological transformation into radial glia. Thus, these results unveil some of the mechanisms underlying radial glia formation.
Patten
Brooke A
BA
Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Peyrin
Jean Michel
JM
Weinmaster
Gerry
G
Corfas
Gabriel
G
D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development; D018920:Coculture Techniques; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005347:Fibroblasts / Q000166:cytology; D005799:Genes, Dominant; D017930:Genes, Reporter; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D066247:Receptor, ErbB-4; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D066246:ErbB Receptors; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; C490174:Fabp7 protein, rat; C497763:Notch1 protein, rat; C587691:Erbb4 protein, rat