31 October 2018 Biomechanics to unravel the mystery of tissue regeneration

Proud to have been a part of this beautiful work ! In collaboration with Florence Ruggiero’s team, we demonstrated how ColXIV-A regulates the checkerboard basement membrane organization and its biomechanics.

Gene profile of zebrafish fin regeneration offers clues to kinetics, organization and biomechanics of basement membrane.

Pauline Nauroy, Alexandre Guiraud, Julien Chlasta, Marilyne Malbouyres, Benjamin Gillet, Sandrine Hughes, Elise Lambert, and Florence Ruggiero (2018)
Matrix Biol.

Abstract: How some animals regenerate missing body parts is not well understood. Taking advantage of the zebrafish caudal fin model, we performed a global unbiased time-course transcriptomic analysis of fin regeneration. Biostatistics analyses identified extracellular matrix (ECM) as the most enriched gene sets. Basement membranes (BMs) are specialized ECM structures that provide tissues with structural cohesion and serve as a major extracellular signaling platform. Whilethe embryonic formation of BM has been extensively investigated, its regeneration in adults remains poorly studied. We therefore focused on BM gene expression kinetics and showed that it recapitulates many aspects of development. As such, the re-expression of the embryonic col14a1a gene indicated that col14a1a is partof the regeneration-specific program. We showed that laminins and col14a1a genesdisplay similar kinetics and that the corresponding proteins are spatially and temporally controlled during regeneration. Analysis of our CRISPR/Cas9-mediated col14a1a knockout fish showed that collagen XIV-A contributes to timely deposition of laminins.

As changes in ECM organization can affect tissue mechanical properties, we analyzed the biomechanics of col14a1a(-/-) regenerative BM using atomic force microscopy (AFM). Our data revealed a thinner BM accompanied by a substantial increase of the stiffness when compared to controls. Further AFM 3D-reconstructions showed that BM is organized as a checkerboard made of alternation of soft and rigid regions that is compromised in mutants leading to a more compact structure. We conclude that collagen XIV-A transiently acts asa molecular spacer responsible for BM structure and biomechanics possibly by helping laminins integration within regenerative BM.


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