Autonomous and non-autonomous regulation of mammalian neurite development by Notch1 and Delta1.
BACKGROUND
On the basis of experiments suggesting that Notch and Delta have a role in axonal development in Drosophila neurons, we studied the ability of components of the Notch signaling pathway to modulate neurite formation in mammalian neuroblastoma cells in vitro.


RESULTS
We observed that N2a neuroblastoma cells expressing an activated form of Notch, Notch1(IC), produced shorter neurites compared with controls, whereas N2a cell lines expressing a dominant-negative Notch1 or a dominant-negative Delta1 construct extended longer neurites with a greater number of primary neurites. We then compared the effects on neurites of contacting Delta1 on another cell and of overexpression of Delta1 in the neurite-extending cell itself. We found that N2a cells co-cultured with Delta1-expressing quail cells produced fewer and shorter neuritic processes. On the other hand, high levels of Delta1 expressed in the N2a cells themselves stimulated neurite extension, increased numbers of primary neurites and induced expression of Jagged1 and Notch1.


CONCLUSIONS
These studies show that Notch signals can antagonize neurite outgrowth and that repressing endogenous Notch signals enhances neurite outgrowth in neuroblastoma cells. Notch signals therefore act as regulators of neuritic extension in neuroblastoma cells. The response of neuritic processes to Delta1 expressed in the neurite was opposite to that to Delta1 contacted on another cell, however. These results suggest a model in which developing neurons determine their extent of process outgrowth on the basis of the opposing influences on Notch signals of ligands contacted on another cell and ligands expressed in the same cell.
Franklin
J L
JL
Department of Molecular Pharmacology/Biological Chemistry, Northwestern University Medical School, Northwestern University Institute for Neuroscience, Chicago 60611, USA.
Berechid
B E
BE
Cutting
F B
FB
Presente
A
A
Chambers
C B
CB
Foltz
D R
DR
Ferreira
A
A
Nye
J S
JS
D000818:Animals; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008959:Models, Neurological; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure*; D009447:Neuroblastoma / Q000235:genetics / Q000648:ultrastructure; D011506:Proteins / Q000235:genetics / Q000502:physiology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; C064045:delta protein