Contact-dependent inhibition of cortical neurite growth mediated by notch signaling.
The exuberant growth of neurites during development becomes markedly reduced as cortical neurons mature. In vitro studies of neurons from mouse cerebral cortex revealed that contact-mediated Notch signaling regulates the capacity of neurons to extend and elaborate neurites. Up-regulation of Notch activity was concomitant with an increase in the number of interneuronal contacts and cessation of neurite growth. In neurons with low Notch activity, which readily extend neurites, up-regulation of Notch activity either inhibited extension or caused retraction of neurites. Conversely, in more mature neurons that had ceased their growth after establishing numerous connections and displayed high Notch activity, inhibition of Notch signaling promoted neurite extension. Thus, the formation of neuronal contacts results in activation of Notch receptors, leading to restriction of neuronal growth and a subsequent arrest in maturity.
Sestan
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N
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Artavanis-Tsakonas
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S
Rakic
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P
D000818:Animals; D002450:Cell Communication; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D003260:Contact Inhibition; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D016501:Neurites / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors; D015533:Transcriptional Activation; D015854:Up-Regulation
D008024:Ligands; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D014157:Transcription Factors