Rapid Homeostatic Turnover of Embryonic ECM during Tissue Morphogenesis

Abstract

The extracellular matrix (ECM) is a polymer network hypothesized to form a stable cellular scaffold. While the ECM can undergo acute remodeling during embryogenesis, it is experimentally difficult to determine whether basal turnover is also important. Most studies of homeostatic turnover assume an initial steady-state balance of production and degradation and measure half-life by quantifying the rate of decay after experimental intervention (e.g., pulse labeling). Here, we present an intervention-free approach to mathematically model basal ECM turnover during embryogenesis by exploiting our ability to live image de novo ECM development in Drosophila to quantify production from initiation to homeostasis. This reveals rapid turnover (half-life ∼7-10 h), which we confirmed by in vivo pulse-chase experiments. Moreover, ECM turnover is partially dependent on proteolysis and network interactions, and slowing turnover affects tissue morphogenesis. These data demonstrate that embryonic ECM undergoes constant replacement, which is likely necessary to maintain network plasticity to accommodate growth and morphogenesis.

Keywords: Collagen; Matrix metalloprotease; Nidogen; Perlecan; basement membrane; embryogenesis; extracellular matrix; mathematical modeling; morphogenesis; turnover.