Distinct dynamics of the extracellular matrix during heart regeneration in different Astyanax mexicanus populations

Presentation of poster 1718B at TAGC 2020 Online. File includes a PDF of the poster (Filename: ZHILIAN HU TAGC2020_USA poster.PDF).


We use Astyanax mexicanus (surface fish and Pachón) to unravel molecular mechanisms of extracellular matrix (ECM) underlying the injured heart. This is based on the distinct regenerative capacity of Astyanax mexicanus in response to the injury: Surface fish can regenerate the ablated heart tissue, similar to zebrafish, while Pachón cannot and instead forms a permanent scar with excess ECM such as collagens, similar to human.

Thecontent, relative proportion, and spatial arrangement of ECM play a pivotal role during tissue regeneration. Any changes in ECM deposition can have a big impact on the ability to regenerate. Astyanax mexicanusallows us to identify the differences in ECM deposition and to identify key players to switch between a degradable scar in a regenerative setting and a permanent scar in a non-regenerative setting.

Our results showed ECM components and their regulating Matrix metalloproteinases (MMPs) are dynamically and differentially expressed during heart regeneration between surface fish and Pachón. Our RNA sequencing data were further validated by quantitative qPCR and RNAscope during the regenerative time window. Wewill link these key scarring differences directly to both the genome and the ability for heart regeneration using new and prior Quantitative Trait Loci analyses. This will allow to find the most fundamental molecular mechanisms directing the wound healing process towards regeneration versus scarring, and to facilitate to the further studies in mammalian models.