Cell cycle and cell determination

Our principal axis of research activity is centred on the relationship between cell fate acquisition and the cell cycle. 

We are interested on the temporal control of cell identity in proliferative cells. How is cell identity determined over time? How are cell proliferation and cell identity coordinated? Understand the complex links between cell fate acquisition and cell proliferation is essential to define the mechanisms underlying developmental processes as well as the generation of diverse pathologies. We use Drosophila as a model system to approach the problem with combined genetic, cellular and molecular biology techniques as well as real-time imaging methodology. In particular, we make extensive use of the developmentally regulated bristle cell lineage that gives rise to external sensory organs on the thorax of the fly.

Due to the evolutionary conservation of basic biological processes, the principles of cell lineage shaping that we have revealed are likely to be extensively conserved in animal development

Highlights

Over the last years, we have shown that:

(1) the Notch-pathway, the main signalling pathway in external sensory organs of Drosophila, and Prospero, a fate determinant, maintain the terminal cells in a quiescent state. As such, in terminal cells, fate acquisition and cell cycle progression are regulated by two parallel mechanisms acting simultaneously.

(2) Escargot and Scratch, two transcription factors belonging to the Snail superfamily, act redundantly to maintain neural precursor cell commitment of progenitor cells as well as to regulate neuronal differentiation.

(3) Cyclin-A, contrary to current belief, is involved in endocycle dynamics in Drosophila. In addition, we show that CycA controls DNA-replication via a subnuclear relocalisation of pre-replication complex.

(4) sensory organ precursor cells, arrested in G2 phase, transit from a self-renewal mode of cell proliferation to a terminal pattern. This highlight the role that developmental G2 phase arrest plays in synchronizing different modes of cell division with signals promoting terminal cell differentiation.

Future directions

Cell cycle and cell polarity.

Cell fate diversity is partly generated by asymmetric cell divisions, in which precursor cells polarize and divide to produce two daughter cells with different developmental fates. Mechanisms controlling the polarization of precursor cells are fairly well studied, however, those that coordinate cell division progression and cell polarization remain largely unknown. In the cell lineage leading to the formation of sensory bristles in Drosophila, we have observed genetic interactions between factors that control cell division and those involved in cell polarity. These data are the basis for a research project that constitutes a main axe of our activity in the near future. We are confident that these very promising observations may reveal links between the processes controlling cell proliferation, polarisation of cell determinants and tissue morphogenesis.

Analysis of the control of neuronal identity by microRNAs

The generation of different cell types is essential for the development of multicellular organisms. Recent experiments show the key role of microRNAs in the mechanisms regulating the temporal synchronization of cell determination and differentiation. The objective of this project is to analyse the role of microRNAs in the control of neuronal fate.

Mechanosensory bristles in adult Drosophila are a model system for studying the mechanisms controlling cell fate. In this system, we have evidences showing the involvement of microRNAs in the control of cell identities. We propose (1) to analyse the phenotype induced by the loss and gain of function of several miRNA candidates that are known to affect neuronal fate and (2) to identify the target genes involved in the control of cell identities. This will be done through an approach that combines cellular and molecular biology, genetics and in vivo imaging methodologies. This project involves the analysis of fundamental processes related to the acquisition of neuronal identity, conserved during evolution mechanism. This ensures that this research will be of general interest to the biology community.

Collaborations

  • Shelagh D. Campbell, Department of Biological Sciences, University of Alberta, Edmonton, Canada
  • Frédérique Peronnet, UMR 7622. Laboratoire de Biologie du Développement CNRS- UPMC.
  • Ghislaine Gayraud and Pascal Moyal, Laboratory of Applied Mathematics (LMAC-UTC), Compiegne,