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XB-JOB-1175
HD/Ddoctoral Position in Marseille (#1)
Lab Kodjabachian Lab Closing Date 2019-06-28
Employer Name Kodjabachian Lab, IBDML, CNRS, Aix-Marseille Universite Posting Date 2019-05-16
Employer URL http://www.ibdm.univ-mrs.fr/equipe/biology-of-ciliated-epithelia/ Salary
Contact None    
Location France,  ,  Marseille cedex 9    
Submit Email laurent.kodjabachian@univ-amu.fr    

Job Description

Molecular control of intercellular junction remodeling during radial intercalation
Scientific background

The insertion of individual mesenchymal cells into an epithelial sheet (radial intercalation) occurs during embryonic development, adult tissue homeostasis, and dissemination of metastatic carcinoma cells. Nevertheless, its control mechanisms remain poorly understood. In particular, little attention has been devoted to the role played by the -accepting- epithelial cells.

The epithelium of the amphibian Xenopus laevis is a simple and accessible model system to study radial intercalation. During the development of this tissue, mesenchymal multiciliated cells (MCCs) undergo a short apical migration to intercalate into an epithelial layer in correspondence of junctions among at least three cells (aka vertices).

Objectives

In this PhD project, it is proposed to investigate the role played by outer layer epithelial cell cytoskeleton and intercellular junctions in the process of MCC intercalation. We have recently identified the signal triggered by the tyrosine kinase receptor KIT and its ligand SCF as a guidance system that controls the directionality of MCC movements during the intercalation process and their correct homing to outer layer vertices. KIT is expressed in intercalating MCCs, while outer layer cells express a transmembrane form of SCF. The PhD candidate will investigate whether a cell-autonomous signal initiated by SCF plays a role in opening outer layer intercellular junctions to accommodate intercalating MCCs.

Methods

Antibodies and custom-made fluorescent reporter constructs under the control of the outer layer-specific promoter of Xenopus nectin will be used to monitor the status of intercellular junctions and cytoskeletal components at different time points during the process of MCC intercalation through time-lapse confocal microscopy. Constructs coding for dominant-negative forms of cytoskeletal or intercellular junction proteins will be used to assess the role of these structures in MCC intercalation. To explore the possibility that SCF is cell-autonomously required for opening the outer-layer intercellular junctions, we will use nectin promoter-based fluorescent reporter constructs to study the dynamics of cytoskeleton and intercellular junctions following morpholino-mediated depletion of SCF.

Impact

The results obtained will clarify the contribution of epithelial cells to the process of

radial intercalation of mesenchymal cells, and shed new light on the mechanisms underlying signaling by the SCF/KIT pathway during development and metastasis.

Expected profile of the PhD candidate

The PhD candidate must have a strong background in one or several of the following disciplines: cell biology, developmental biology, biochemistry, biophysics. He or she must have a keen interest for quantitative biology and real-time imaging.

Contact: laurent.kodjabachian@univ-amu.fr


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