Dual Control of Neurogenesis by PC3 Through Cell Cycle Inhibition and Induction of Math1

Overview

Journal J Neurosci

Specialty Neurology

Date 2004 Apr 2

PMID 15056715

Citations 38

Authors

Daniela Canzoniere

Stefano Farioli-Vecchioli

Filippo Conti

Maria Teresa Ciotti

Ada Maria Tata

Gabriella Augusti-Tocco

Elisabetta Mattei

Madepalli K Lakshmana

Valery Krizhanovsky

Steven A Reeves

Roberto Giovannoni

Francesca Castano

Antonio Servadio

Nissim Ben-Arie

Felice Tirone

Affiliations

Soon will be listed here.

Abstract

Growing evidence indicates that cell cycle arrest and neurogenesis are highly coordinated and interactive processes, governed by cell cycle genes and neural transcription factors. The gene PC3 (Tis21/BTG2) is expressed in the neuroblast throughout the neural tube and inhibits cell cycle progression at the G1 checkpoint by repressing cyclin D1 transcription. We generated inducible mouse models in which the expression of PC3 was upregulated in neuronal precursors of the neural tube and of the cerebellum. These mice exhibited a marked increase in the production of postmitotic neurons and impairment of cerebellar development. Cerebellar granule precursors of PC3 transgenic mice displayed inhibition of cyclin D1 expression and a strong increase in the expression of Math1, a transcription factor required for their differentiation. Furthermore, PC3, encoded by a recombinant adenovirus, also induced Math1 in postmitotic granule cells in vitro and stimulated the Math1 promoter activity. In contrast, PC3 expression was unaffected in the cerebellar primordium of Math1 null mice, suggesting that PC3 acts upstream to Math1. As a whole, our data suggest that cell cycle exit of cerebellar granule cell precursors and the onset of cerebellar neurogenesis are coordinated by PC3 through transcriptional control of cyclin D1 and Math1, respectively.

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