ECM-regulator timp is required for stem cell niche organization and cyst production in the Drosophila ovary

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.This work was funded by the Spanish MINECO (Grants BFU2009-08013, BFU2012-35446 to AGR, BFU2010-16669 to MDMB and Consolider CSD-2007-00008 to MDMB and AGR), by the Junta de Andalucía (Proyecto de Excelencia P09-CVI-5058 to MDMB and AGR) and by the European Regional Development Fund (FEDER). JRP was supported by a JAE-Doc contract from the Spanish National Research Council (CSIC) and KF by a Career Development Award from the UK Medical Research Council.Peer Reviewe