Notch1 inhibits neurite outgrowth in postmitotic primary neurons

O. Berezovska, Pamela J McLean, R. Knowles, M. Frosh, F. M. Lu, S. E. Lux, B. T. Hyman

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Notch plays an important role in cell fate decisions in uncommitted proliferative cells, including neurogenesis, but is believed to not have a role in postmitotic cells. We have shown previously that Notch1 is highly expressed in embryonal mouse and human brain, but surprisingly it continues to be expressed at low levels in the adult brain. The function of Notch1 in postmitotic neurons in mammals is unknown. To better understand the potential role of Notch1 in mature central nervous system neurons we studied the effect of Notch1 transfection on neurite outgrowth in primary neocortex hippocampal neurons. Transfection at two days in vitro with full length Notch1 inhibited neurite outgrowth. Transfection at five to six days in vitro, after neurite outgrowth was established, led to apparent regression of neurites. These effects were enhanced when truncated constitutively active forms of Notch1 were introduced. Co-transfection with Numb, a physiological inhibitor of Notch, blocked Notch's effect on neurite outgrowth. We also examined whether Notch1 could activate C-promoter binding factor (CBF1) transcription factor using C-promoter binding factor-luciferase constructs, and demonstrated that this signal transduction pathway is present and can be activated in postmitotic neurons.Our results show that in postmitotic neurons Notch1 influences neurite morphology, and can activate its native signal transduction pathway. These data strongly suggest that Notch1 may play a physiologically important role in the central nervous system beyond neurogenesis. Copyright (C) 1999 IBRO.

Original languageEnglish (US)
Pages (from-to)433-439
Number of pages7
JournalNeuroscience
Volume93
Issue number2
DOIs
StatePublished - Jul 1999
Externally publishedYes

Fingerprint

Transfection
Neurons
Neurogenesis
Neurites
Signal Transduction
Central Nervous System
Neocortex
Brain
Luciferases
Mammals
Transcription Factors
Neuronal Outgrowth
In Vitro Techniques

Keywords

  • CBF1
  • Neurite outgrowth
  • Notch1
  • Numb
  • Primary neurons
  • Transfection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Berezovska, O., McLean, P. J., Knowles, R., Frosh, M., Lu, F. M., Lux, S. E., & Hyman, B. T. (1999). Notch1 inhibits neurite outgrowth in postmitotic primary neurons. Neuroscience, 93(2), 433-439. https://doi.org/10.1016/S0306-4522(99)00157-8

Notch1 inhibits neurite outgrowth in postmitotic primary neurons. / Berezovska, O.; McLean, Pamela J; Knowles, R.; Frosh, M.; Lu, F. M.; Lux, S. E.; Hyman, B. T.

In: Neuroscience, Vol. 93, No. 2, 07.1999, p. 433-439.

Research output: Contribution to journalArticle

Berezovska, O, McLean, PJ, Knowles, R, Frosh, M, Lu, FM, Lux, SE & Hyman, BT 1999, 'Notch1 inhibits neurite outgrowth in postmitotic primary neurons', Neuroscience, vol. 93, no. 2, pp. 433-439. https://doi.org/10.1016/S0306-4522(99)00157-8
Berezovska, O. ; McLean, Pamela J ; Knowles, R. ; Frosh, M. ; Lu, F. M. ; Lux, S. E. ; Hyman, B. T. / Notch1 inhibits neurite outgrowth in postmitotic primary neurons. In: Neuroscience. 1999 ; Vol. 93, No. 2. pp. 433-439.
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