Abstract
The extracellular matrix (ECM) is a pivotal component adult tissues and of many tissue-specific stem cell niches. It provides structural support and regulates niche signaling during tissue maintenance and regeneration. In many tissues, ECM remodeling depends on the regulation of MMP (matrix metalloproteinase) activity by inhibitory TIMP (tissue inhibitors of metalloproteinases) proteins. Here, we report that the only Drosophila timp gene is required for maintaining the normal organization and function of the germline stem cell niche in adult females. timp mutant ovaries show reduced levels of both Drosophila Collagen IV α chains. In addition, tissue stiffness and the cellular organization of the ovarian niche are affected in timp mutants. Finally, loss of timp impairs the ability of the germline stem cell niche to generate new cysts. Our results demonstrating a crucial role for timp in tissue organization and gamete production thus provide a link between the regulation of ECM metabolism and tissue homeostasis.
Highlights
The extracellular matrix (ECM) is an essential component of adult stem cell niches, and a fundamental player in tissue homeostasis, as it regulates stem cell fate by mediating signal delivery and by providing matrix-directed differentiation [1, 2]
The extracellular matrix (ECM) offers signals and support to stem cell niches, local microenvironments that provide these cells with necessary factors for their survival
Because the repair of damaged tissue or the replenishment of cell lineages in functional organs requires significant cellular rearrangements, ECM remodeling has to be tightly coordinated with stem cell niche activity
Summary
The extracellular matrix (ECM) is an essential component of adult stem cell niches, and a fundamental player in tissue homeostasis, as it regulates stem cell fate by mediating signal delivery and by providing matrix-directed differentiation [1, 2]. Matrix metalloproteinases (MMPs) are a class of well-known proteolytic enzymes that are able to degrade most ECM components and promote ECM turnover [4, 5]. Because of their functions in ECM remodeling, MMPs play key roles in development and regeneration, as shown for branching morphogenesis, angiogenesis and wound healing [6]. The control of stem cell proliferation by MMP activity has been recently reported in the ovarian niche in Drosophila, underscoring the importance of ECM metabolism in stem cell niche regulation [10]
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