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A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination

In this report, we have examined the requirement for the retinoblastoma (Rb) gene family in neuronal determination with a focus on the developing neocortex. To determine whether pRb is required for neuronal determination in vivo, we crossed the Rb−/− mice with transgenic mice expressing β-galactosid...

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Autores principales: Slack, Ruth S., El-Bizri, Hiba, Wong, Josée, Belliveau, Daniel J., Miller, Freda D.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132670/
https://www.ncbi.nlm.nih.gov/pubmed/9508781
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author Slack, Ruth S.
El-Bizri, Hiba
Wong, Josée
Belliveau, Daniel J.
Miller, Freda D.
author_facet Slack, Ruth S.
El-Bizri, Hiba
Wong, Josée
Belliveau, Daniel J.
Miller, Freda D.
author_sort Slack, Ruth S.
collection PubMed
description In this report, we have examined the requirement for the retinoblastoma (Rb) gene family in neuronal determination with a focus on the developing neocortex. To determine whether pRb is required for neuronal determination in vivo, we crossed the Rb−/− mice with transgenic mice expressing β-galactosidase from the early, panneuronal Tα1 α-tubulin promoter (Tα1:nlacZ). In E12.5 Rb−/− embryos, the Tα1:nlacZ transgene was robustly expressed throughout the developing nervous system. However, by E14.5, there were perturbations in Tα1:nlacZ expression throughout the nervous system, including deficits in the forebrain and retina. To more precisely define the temporal requirement for pRb in neuronal determination, we functionally ablated the pRb family in wild-type cortical progenitor cells that undergo the transition to postmitotic neurons in vitro by expression of a mutant adenovirus E1A protein. These studies revealed that induction of Tα1:nlacZ did not require proteins of the pRb family. However, in their absence, determined, Tα1:nlacZ-positive cortical neurons underwent apoptosis, presumably as a consequence of “mixed signals” deriving from their inability to undergo terminal mitosis. In contrast, when the pRb family was ablated in postmitotic cortical neurons, there was no effect on neuronal survival, nor did it cause the postmitotic neurons to reenter the cell cycle. Together, these studies define a critical temporal window of requirement for the pRb family; these proteins are not required for induction of neuronal gene expression or for the maintenance of postmitotic neurons, but are essential for determined neurons to exit the cell cycle and survive.
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spelling pubmed-21326702008-05-01 A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination Slack, Ruth S. El-Bizri, Hiba Wong, Josée Belliveau, Daniel J. Miller, Freda D. J Cell Biol Article In this report, we have examined the requirement for the retinoblastoma (Rb) gene family in neuronal determination with a focus on the developing neocortex. To determine whether pRb is required for neuronal determination in vivo, we crossed the Rb−/− mice with transgenic mice expressing β-galactosidase from the early, panneuronal Tα1 α-tubulin promoter (Tα1:nlacZ). In E12.5 Rb−/− embryos, the Tα1:nlacZ transgene was robustly expressed throughout the developing nervous system. However, by E14.5, there were perturbations in Tα1:nlacZ expression throughout the nervous system, including deficits in the forebrain and retina. To more precisely define the temporal requirement for pRb in neuronal determination, we functionally ablated the pRb family in wild-type cortical progenitor cells that undergo the transition to postmitotic neurons in vitro by expression of a mutant adenovirus E1A protein. These studies revealed that induction of Tα1:nlacZ did not require proteins of the pRb family. However, in their absence, determined, Tα1:nlacZ-positive cortical neurons underwent apoptosis, presumably as a consequence of “mixed signals” deriving from their inability to undergo terminal mitosis. In contrast, when the pRb family was ablated in postmitotic cortical neurons, there was no effect on neuronal survival, nor did it cause the postmitotic neurons to reenter the cell cycle. Together, these studies define a critical temporal window of requirement for the pRb family; these proteins are not required for induction of neuronal gene expression or for the maintenance of postmitotic neurons, but are essential for determined neurons to exit the cell cycle and survive. The Rockefeller University Press 1998-03-23 /pmc/articles/PMC2132670/ /pubmed/9508781 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Slack, Ruth S.
El-Bizri, Hiba
Wong, Josée
Belliveau, Daniel J.
Miller, Freda D.
A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination
title A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination
title_full A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination
title_fullStr A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination
title_full_unstemmed A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination
title_short A Critical Temporal Requirement for the Retinoblastoma Protein Family During Neuronal Determination
title_sort critical temporal requirement for the retinoblastoma protein family during neuronal determination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132670/
https://www.ncbi.nlm.nih.gov/pubmed/9508781
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