Fiche Projet

Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Nom et prénom du directeur de thèse (et si besoin du) : Coudrier Evelyne,
Le directeur de thèse et le co-directeur doivent impérativement être habilités à diriger les recherches (HDR)
Coordonnées
Tel : 0156246370
e-mail :[email protected]
Nom et prénom du co-directeur : Del Bene Filippo
Coordonnées
Tel : 0156246552
e-mail : [email protected]
Nom et prénom du responsable de l’équipe :
Nombre de chercheurs et enseignants-chercheurs statutaires de l’équipe titulaires d’une HDR :
5
Nom et prénom du responsable du laboratoire : Bruno Goud
Intitulé du laboratoire et N° d’unité : UMR 144
Spécialité : Biologie cellulaire-Biologie du développement
Titre du projet de thèse : Myosin 1b for brain and axonal development
Résumé du projet de thèse (1 page maximum, en anglais)
Like all vertebrate Myosin 1 family members, Myosin 1b (Myo1b) has the capacity to couple
mechanically the membrane with the actin cytoskeleton and generates mechanical forces. We have
previously shown that Myo1b associated with organelles regulates membrane trafficking by controlling
the morphology of these organelles and the formation of branched actin network (Almeida et al. 2011
Nature Cell Biol.). We also demonstrated that isolated Myo1b bound to a PI4,5P2 containing GUV
(Giant Unilamellar Vesicle) can pull membrane tubes out of this GUV along actin bundles immobilized
on a solid substrate (Yamada et al. 2014 Nature Com.). More recently we analyzed the role of Myo1b
associated with the plasma membrane. We have demonstrated that Myo1b regulates the redistribution
of myosin II in acto-myosin fibers and the formation of filopodia induced by EphB2 receptors
stimulation (Prospéri et al. 2015 J. Cell Biol.). Together these data indicate that myosin1b controls
various cellular processes including membrane trafficking and cell migration by linking mechanically
membrane to the actin cytoskeleton and thereby controlling membrane shape.
Our recent data indicate that Myo1b is also required for the formation of axons and the
establishment of neuronal polarity in cultured hippocampal and cortical neurons by controlling the
formation of actin waves. Furthermore, our biochemical data shows that Myo1b can physically interact
with two proteins involved in axon guidance depending on netrin, UNC5 and MAX-1; MAX-1 being a
member of a new protein family characterized by a PH and a FERM domains.
The aim of our project is to reveal Myo1b function for the formation of axons and neuron
polarity in relation with UNC5 and MAX-1 and elucidate the molecular mechanism by which it
achieves its function in vivo. So far we have used as experimental model cultured neurons derived from
post mitotic polarized neurons after dissociation from embryonic brain. Analysis of the polarization of
this cellular model corresponds to the analysis of the repolarization of previously polarized neurons. In
contrast most neurons undergo axon neurite polarization during migration in vivo. Thus, we propose to
study the requirement of myo1b for brain and axonal development in vivo in zebrafish. This project
will exploit the combination of cell biology approaches and genetic approaches that are currently
developed in Evelyne Coudrier’s (Institut Curie UMR 144) and Filippo Del Bene’s (Institut Curie
UMR 3215) teams. We have already generated a zebrafish loss-of-function model of Myo1b and we
aim now to analyzed its phenotype in the initial axonal development in retina ganglion cells and in
primary motoneurons, two cellular types for which we have the proper genetic tools to allow imaging
studies and cellular dynamics in vivo. In particular we will analyze the consequence of Myo1b loss or
overexpression of different mutated forms on initial axonal polarization, actin flow and endocytic
compartment trafficking. Together these data will allow the establishment of Myo1b role in neuronal
polarization and axonal extension.
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Thèses actuellement en cours dans l’équipe
Nom et Prénom du doctorant
Olga Iuliano
Amal Kasri
Guillaume Kulakowski
Camilla Barros
Charlotte Alibert
Bruno Latche
Nom du directeur de thèse
Evelyne coudrier
Bruno Goud -Stephanie
Miserey (CR1)
Bruno Goud -Stephanie
Miserey (CR1)
Kristin Schauer (HDR)
Jean Batiste Menneville
(HDR)
Kristin Schauer
Année de 1ere
inscription et
Ecole Doctorale
2011
2014
Financement pendant la thèse
Institut Curie
Paris VI
2014
ERC
2014
2014
sciencia sem fronteras ( financement
du gouvernement brésilien)
Paris VI programme IPV
2014
PSL
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.
Prosperi, M.T., Lepine P., Dingli F., Paul-Gilloteaux P., Martin R., Loew D., Knolker H.J., and
Coudrier E. 2015. Myosin 1b functions as an effector of EphB signaling to control cell
repulsion. J Cell Biol. 210:347-361.
Yamada, A., Mamane A., Lee-Tin-Wah J., Di Cicco J., Prévost C., Lévy D., Joanny J.-F.,
Coudrier E., and Bassereau B. 2014. Catch bond behavior facilitates membrane tubulation
by
a non-processive myosin 1b Nature Communications. Apr 7;5:3624
Dunn TW, Gebhardt C, Naumann EA, Riegler C, Ahrens MB, Engert F, Del Bene F. 2016
Neural Circuits Underlying Visually Evoked Escapes in Larval Zebrafish. Neuron Feb
3;89(3):613-28.
Docteurs encadrés par le directeur de thèse ayant soutenu après
septembre 2010 et publications relatives à leur sujet de thèse. Mettre en gras le nom du
directeur de thèse et celui du docteur.
Nom Prénom : Lépine Priscilla
25/09/3013
Date de soutenance :
Durée de thèse (en mois): 36
Ecole Doctorale : CDV-ED515
Publication :
-Prosperi, M.T.*, Lepine P.*, Dingli F., Paul-Gilloteaux P., Martin
R., Loew D., Knolker H.J., and Coudrier E. 2015. Myosin 1b
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
functions as an effector of EphB signaling to control cell repulsion.
J Cell Biol. 210:347-361
-Lépine P., Revenu C. Prospéri MT, Del Bene F. Coudrier E.
Myosin1b regulates the development of the intestinal epithelium in
zebrafish (manuscrit soumis)
Nom Prénom : Thomas Auer
30/09/2014
Date de soutenance :
Durée de thèse (en mois): 36
Ecole Doctorale : Heidelberg
University Germany (cotutelle Dr. Filippo Del Bene avec Prof. Jochen
Wittbrodt)
Publications :
-Auer TO, Xiao T, Bercier V, Gebhardt C, Duroure K, Concordet
JP, Wyart C, Suster M, Kawakami K, Wittbrodt J, Baier H, Del
Bene F. Deletion of Kinesin I motor unmasks a mechanism of
homeostatic branching control by Neurtrophin-3. eLIFE 2015 Jun
15;4
- Auer TO, Duroure K, Concordet JP, Del Bene F CRISPR/Cas9mediated conversion of eGFP into Gal4 transgenic lines in
zebrafish. Nature Protocols 2014 Dec;9(12):2823-40.
- Auer TO, Duroure K, De Cian A, Concordet JP, Del Bene F
(2014) Highly efficient CRISPR/Cas9-mediated knock-in in
zebrafish by homology-independent DNA repair. Genome research
24:142-153
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