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Thesis defense: Pauline NAUROY

When Nov 02, 2017
from 02:00 PM to 05:00 PM
Contact Name
Contact Phone 04 2673 1357
Attendees Dr. Anna Jaźwińska, Université de Fribourg, Suisse Rapporteur
Pr. Manuel Koch, Université de Cologne, Allemagne Rapporteur
Pr. Sophie Vriz, Collège de France, France Examinateur
Dr. Alexander Nyström, Université de Fribourg, Allemagne Examinateur
Dr. Florence Ruggiero, Université de Lyon, France Directrice de thèse

On 2nd of November Pauline NAUROY from team of Florence RUGGIERO ("Extracellular matrix biology and pathology") will defend her thesis entitled: 

 

Extracellular matrix proteins in regeneration:

A study using the zebrafish caudal fin model

 

This event is scheduled at 02:00 PM in Amphi Bio (ENS, Monod campus).

 

Abstract:

 

In addition to their structural role in tissues, extracellular matrix (ECM) proteins are implicated in various biological events and signaling pathways. Surprisingly, their implication in regeneration remains poorly documented. My PhD project aimed at filling this gap.

 

To determine the ECM players of regeneration, I thus took advantage of the adult zebrafish caudal fin model for it shows unique advantages. To explore the ECM landscape and its dynamics during regeneration, I first performed a time-course transcriptomic analysis using RNA-seq. Because no list was available to comprehensively annotate ECM genes in zebrafish, I first characterized the zebrafish matrisome, defined as the list of ECM and ECM-related genes. For that, we developed an in silico orthology-based method and validated the robustness of our approach using various independent strategies.

 

Bioinformatics analyses of RNA-seq data revealed that among the 4,000 genes differentially expressed during regeneration, the most enriched gene sets are related to ECM. I then analyzed epidermal basement membrane (BM) gene expression profiles during regeneration, a specialized ECM structure that provides tissues with structural cohesion and serves as a signaling platform. In addition to “BM master components”, other ECM genes of the BM zone whose function remains elusive were found in our transcriptome. Among them was col14a1a, encoding collagen XIV-A protein, whose expression was shown to be restricted to embryos. Collagen XIV-A is re-expressed by epidermal basal cells and progressively deposited in the BM zone as the fin regenerates. Using atomic force microscopy, we showed that vivo-morpholino knockdown of collagen XIV-A resulted in a thinner and stiffer BM. These results were confirmed in a zebrafish collagen XIV-A knockout line that I have generated using the CRISPR/Cas9 technology. Altogether our results indicated that collagen XIV-A is a new regulator of the BM biomechanics probably by acting as a molecular spacer that is transiently but specifically required for the proper three-dimensional organization of the BM during regeneration.

 

My PhD work represents the first documentation of ECM gene expression profiles of regeneration and underscores the importance of collagen XIV-A in the epidermal BM regeneration. As such, our findings will certainly open new avenues of investigation in regenerative and reconstructive medicine.

 

Key words:

zebrafish, regeneration, matrisome, extracellular matrix, basement membrane, collagen XIV