Cell Cycle and Development
Themes and areas of research : Quantitative biology and modeling , Development and evolution , Cellular dynamics and signaling , Genome and chromosome dynamics , Models , Molecular and cellular pathologies
Our group is interested in the molecular mechanisms that control the cell cycle machinery during development.
Control of the cell cycle is a fundamental aspect of cell biology. Such control is essential for the normal development of an organism, which requires a precise orchestration of cell proliferation, cell differentiation and morphogenesis. Breakdown of cell cycle control has drastic consequences and leads to cell death, genome instability or deregulated growth, typical of cancer.
Despite considerable advances in our understanding of the mechanisms of cell cycle progression in single cells, much less is known about the coordination of the cell cycle and development in a multicellular context. For example, in the early C. elegans embryo, asymmetric cell divisions produce descendants whose cell cycle durations are different (Figure 1). This asynchrony appears essential for proper cell fate determination and normal development. Nevertheless, how this asynchrony is established and maintained during embryogenesis is poorly understood; the nature of the signaling events and targeted cell cycle components is still largely unknown.
Our goal is to shed light on the molecular mechanisms governing cell cycle division during animal development. We are using as a model system the nematode C. elegans, since this organism provides a powerful setting in which cell cycle control can be genetically analyzed during development by combining cell biology techniques and proteomics. More specifically, we are investigating the role and regulation of Cullin-RING ubiquitin-ligases (CRLs) during C. elegans development. CRLs are the largest family of ubiquitin-ligases, and its members selectively target diverse protein substrates such as cell cycle regulators for ubiquitin-dependent degradation by the 26S proteasome (Figure 2). Although the molecular composition of CRLs is beginning to emerge (Figure 3), only a small subset of substrates has as yet been identified.
We are focusing our research on the following questions:
- What are the functions of CRLs during C. elegans development' What are their critical substrates and the function of these substrates'
- How are CRLs regulated'
- What is the molecular basis for distinct cell cycle duration in the early C. elegans embryo?
These studies, in which we aim to identify the basic molecular mechanisms that control cell cycle division in the context of animal development, are critical to our understanding of both development and oncogenesis.
Selection of Publications
Cyclin A-cdk1-Dependent Phosphorylation of Bora Is the Triggering Factor Promoting Mitotic Entry.
Vigneron, S., Sundermann, L., Labbé, J. C., Pintard, L., Radulescu, O., Castro, A., and Lorca, T.
Dev Cell. 2018 45, 637-650.e7.
Channel Nucleoporins Recruit PLK-1 to Nuclear Pore Complexes to Direct Nuclear Envelope Breakdown in C. elegans.
Martino, L., Morchoisne-Bolhy, S., Cheerambathur, D. K., Van Hove, L., Dumont, J., Joly, N., Desai, A., Doye, V., and Pintard, L.
Dev Cell. 2017 43, 157-171.e7.
A Single-Cell Biochemistry Approach Reveals PAR Complex Dynamics during Cell Polarization.
Dickinson, D. J., Schwager, F., Pintard, L., Gotta, M., and Goldstein, B.
Dev Cell. 2017 42, 416-434.e11.
Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells.
Thomas, Y., Cirillo, L., Panbianco, C., Martino, L., Tavernier, N., Schwager, F., Van Hove, L., Joly, N., Santamaria, A., Pintard, L., and Gotta, M.
Cell Rep. 2016 5, 510-518.
Microtubule-severing activity of the AAA+ ATPase Katanin is essential for female meiotic spindle assembly.
Joly, N., Martino, L., Gigant, E., Dumont, J., and Pintard, L.
Development. 2016 143, 3604-3614.
RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery in Caenorhabditis elegans.
Ossareh-Nazari, B., Katsiarimpa, A., Merlet, J., and Pintard, L.
G3 (Bethesda). 2016 6,3431-3442
Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos.
Tavernier N, Noatynska A, Panbianco C, Martino L, Van Hove L, Schwager F, Léger T, Gotta M, Pintard L.
J Cell Biol. 2015 Mar 16;208(6):661-9
Microtubule severing by the katanin complex is activated by PPFR-1-dependent MEI-1 dephosphorylation.
Gomes JE, Tavernier N, Richaudeau B, Formstecher E, Boulin T, Mains PE, Dumont J, Pintard L.
J Cell Biol.2013 Aug 5;202(3):431-9.
CRL2LRR-1 E3-Ligase Regulates Proliferation and Progression through Meiosis in the Caenorhabditis elegans Germline. Burger J, Merlet J, Tavernier N, Richaudeau B, Arnold A, Ciosk R, Bowerman B, Pintard L.
PLoS Genetics.2013 Mar; 9(3):e1003375.