Ecole doctorale "LOGIQUE DU VIVANT

Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Nom et prénom du directeur de thèse (et si besoin du co-directeur) : Agnes AUDIBERT
Le directeur de thèse et le co-directeur doivent impérativement être habilités à diriger les recherches (HDR)
Coordonnées
Tel : 01 44 27 22 49
e-mail : [email protected]
Nom et prénom du responsable de l’équipe : Michel GHO
Nombre de chercheurs et enseignants-chercheurs statutaires de l’équipe titulaires d’une HDR : 3
Nom et prénom du responsable du laboratoire : Sylvie Schneider-Maunoury
Intitulé du laboratoire et N° d’unité : Laboratoire de Biologie du développement ; UMR7622
Spécialité : Biologie du développement ; biologie cellulaire
Titre du projet de thèse : Coordination between cell cycle, cell polarity and cell determination during
Drosophila development.
Résumé du projet de thèse (1 page maximum, en anglais)
Cell proliferation, planar cell polarity and cell determination are fundamental processes for a proper
development and morphogenesis of multi-cellular organisms. A well-known example of this coordination is
asymmetric divisions, which ensure differential segregation of polarized cellular determinants during the mitosis
of precursor cells. Deregulation of these mechanisms is associated with various developmental syndromes as
well as pathologies including cancer. Although molecular mechanisms and regulatory gene networks underlying
each process are well known, those that coordinate these processes remain largely unknown. This research
project proposes to analyze this coordination in the Drosophila bristle cell lineage, which generates the
peripheral nervous system organs. These organs are composed of four cells with distinct morphology and
functions. All of these cells come from asymmetric divisions of a single precursor cell. As such, this first
division generates two sub-lineages, one giving rise to the internal cells and the other one forming the external
structures. Based on original observations, and using in vivo imaging, genetics, molecular and cell biology
approaches, two axes of research will be developed based on two main questions:
1- How could cell cycle factors influence cell polarity and cell determination?
2 - How could cell identity influence the activity of complexes that drive mitotic entry?
In the first axe, two essential factors, controlling cell proliferation, will be analyze: Cyclin A (CycA), a
cyclin essential for the entry into mitosis, and Fizzy related (Fzr) an activator of the ubiquitin ligase complex;
APC/C (APC/C). In the bristle cell lineage, we have observed that a pool of CycA is asymmetrically localized at
the posterior pole of the precursor cells, and that cycA genetically interacts with frizzled, a gene involved in
planar cell polarity. We hypothesize that CycA acts as a bridge linking cell proliferation with cell polarity. To
study this possibility, we will investigate the physiological relevance of the CycA asymmetric cortical
localization and their interaction with frizzled. We will also analyze the molecular mechanism leading to CycA
localization, investigating whether a discrete domain of the CycA allows its location to the cortex and if this
localization is dependent on Cdk1 activity. Concerning Fzr, we have observed, that its gain of function induces
loss of sensory organs. One hypothesis is that a cell fate transformation changes external cells into internal cells.
1
Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Thus, we will analyze precisely this phenotype at cellular level and how Fzr could controlled cell identity.
The second axe is based on preliminary observations showing that the delay to entry into mitosis induced
by cycA loss of function depends on cell identity. We propose to analyze whether Cdk1 activity is dependent on
the cell identity and if so we will study the intriguing possibility that Cdk1 interacts with different cyclins
depending to cell identity.
As such, our project will certainly clarify the mechanism underlying interaction between cell
proliferation and cell determination, a relation that is often deregulated and at the origin of several human
pathologies.
Thèses actuellement en cours dans l’équipe
Nom et Prénom du doctorant
Nom du directeur de thèse
Année de 1ere
inscription et
Ecole Doctorale
Financement pendant la thèse
Trois publications récentes du directeur de thèse (du co-directeur ou du co-encadrant s’il y a lieu).Mettre en gras le nom
du directeur de thèse.
1- Ayeni JO, Audibert A, Fichelson P, Srayko M, Gho M, Campbell SD. G2-phase arrest prevents bristle
progenitor self-renewal and synchronizes cell division with cell fate differentiation. Co-1er auteur.
Development. 2016 Feb 18. pii: dev.134270.
2 - Fernando C, Audibert A, Simon F, Tazi J, Juge F. A rôle for the Serine/Arginine-Rich protein B52/SRSF6 in
cell growth ans Myc expression in Drosophila. Co-1er auteur. Genetics. 2015 Apr;199(4):1201-11.
3- Sallé J, Campbell S, Gho M, Audibert A. (2012) CycA is involved in the control of endoreplication dynamics
in the Drosophila bristle lineage. Development.132. 547-557.
4- Simon F, Fichelson P, Gho M, Audibert A. (2009) Notch and Prospero Repress Proliferation Following
Cyclin E Overexpression in the Drosophila Bristle Lineage. PloS Genetics 5(8): e1000594.
doi:10.1371/journal.pgen.1000594.
5- Remaud S, Audibert A, Gho M. (2008) S-phase favours notch cell responsiveness in the Drosophila bristle
lineage. PLoS One. 3(11):e3646
Docteurs encadrés par le directeur de thèse
Nom Prénom : Jeremy Sallé
Date de soutenance : 29/09/2011
Durée de thèse (en mois): 48
Ecole Doctorale : CDV
Publications : Sallé J, Campbell S, Gho M, Audibert A. (2012) CycA is involved in the control of endoreplication
dynamics in the Drosophila bristle lineage. Development.132. 547-557.
Position actuelle: Post doc à l’institut Jacques Monid, Nicolas Minc Team
En tant que co-directeur de thèse
Nom Prénom : Sylvie Remaud
Date de soutenance : 25/11/2008
Publications :Remaud S, Audibert A, Gho M. (2008) S-phase favours notch cell responsiveness in the Drosophila
bristle lineage. PLoS One. 3(11):e3646
position actuelle : MCU au MNHN.
2