The proneural NeuroG2 drives cell cycle exit of neuronal precursors by specifically repressing a subset of cyclins acting at the G1 and S phases of the cell cycle


  • Fabienne PITUELLO
  • Sophie BEL-VIALAR
  • François MEDEVIELLE

We previously showed that forcing neural progenitors to cycle is not sufficient to prevent differentiation into neurons (Lobjois et al., 2008). Therefore, cell cycle exit is not a prerequisite to neuron differentiation; rather both events need to be coordinated during normal neurogenesis. We now identified the transcriptional program coordinating cell cycle arrest and differentiation (Lacomme et al., 2012): Using a transcriptomic approach designed to identify gene networks modified at the onset of the proneural NEUROG2 expression, we showed that one of the first action of NEUROG2 is to downregulate specifically a subset of cyclins acting at the G1 and S phases of the cell cycle without affecting the expression of associated cyclin-dependent kinases (CDK) or cyclin-dependent kinase inhibitors (CKI). We demonstrated by phenotypic analysis that this rapid repression of cyclins prevents S phase entry of neuronal precursors, thus favoring cell cycle withdrawal. In addition we showed that NEUROG2 can drive neuronal differentiation independently of cell cycle exit indicating that a main function of NEUROG2, in the course of normal development, is to coordinate these two separable events (Lacomme et al., 2012).

Ongoing work

Few years ago we showed that NEUROG2 proneural activity also involves the repression of patterning genes such as the transcription factor PAX6 (Bel-Vialar et al., 2007). We found that this repression is indirect and involve transcriptional arrest. We are currently characterizing regulatory regions controlling PAX6 expression in the neural tube in order to cross our transcriptomic data with in silico analysis to identify the transcription factor involved in this repression downstream of NEUROG2.



Other funding : Université Toulouse 3

Past people involved : M. Lacomme  PhD -2011, post-doctorant fellow IRCM, Montréal

Collaborations: Laurence Liaubet (INRA-Toulouse Castanet) ;  V Van Heyningen (Edimbourg)

Université Paul Sabatier
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31062 TOULOUSE Cedex

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