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PMID: 11027225 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evidence that helix-loop-helix proteins collaborate with retinoblastoma tumor suppressor protein to regulate cortical neurogenesis.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 20 ·2000-10-15 ·Pages 7648-56

Toma JG, El-Bizri H, Barnabe-Heider F, Aloyz R, Miller FD

Abstract

The retinoblastoma tumor suppressor protein (pRb) family is essential for cortical progenitors to exit the cell cycle and survive. In this report, we test the hypothesis that pRb collaborates with basic helix-loop-helix (bHLH) transcription factors to regulate cortical neurogenesis, taking advantage of the naturally occurring dominant-inhibitory HLH protein Id2. Overexpression of Id2 in cortical progenitors completely inhibited the induction of neuron-specific genes and led to apoptosis, presumably as a consequence of conflicting differentiation signals. Both of these phenotypes were rescued by coexpression of a constitutively activated pRb mutant. In contrast, Id2 overexpression in postmitotic cortical neurons affected neither neuronal gene expression nor survival. Thus, pRb collaborates with HLHs to ensure the coordinate induction of terminal mitosis and neuronal gene expression as cortical progenitors become neurons.

MeSH Terms
Adenoviridae/genetics Animals Apoptosis Cell Differentiation/physiology Cell Survival/physiology Cells, Cultured Cerebral Cortex/cytology,embryology,metabolism DNA-Binding Proteins/genetics,metabolism,pharmacology Gene Expression/drug effects Genetic Vectors/genetics,metabolism Helix-Loop-Helix Motifs/physiology In Situ Nick-End Labeling Inhibitor of Differentiation Protein 2 Mice Neurons/cytology,metabolism Repressor Proteins Retinoblastoma Protein/metabolism Stem Cells/cytology,metabolism Transcription Factors/metabolism Transfection Tubulin/metabolism
Chemicals
DNA-Binding Proteins Idb2 protein, mouse Inhibitor of Differentiation Protein 2 Repressor Proteins Retinoblastoma Protein Transcription Factors Tubulin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Toma J G
Center for Neuronal Survival, Montreal Neurological Institute, Montreal, Canada H3A 2B4.
El-Bizri H
Barnabe-Heider F
Aloyz R
Miller F D
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2000-10-15
Pages
7648-56
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772880
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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