Live analysis of Drosophila female germline stem cells reveals a role for ECM-regulator Timp in stem cell division

Abstract

Resumen del póster presentado al 11th Meeting of the Spanish Society for Developmental Biology, celebrado en Girona (España) del 19 al 21 de octubre de 2016.-- Tambien presentado a la 25th European Drosophila Research Conference, celebrada en londres (UK) del 22 al 25 de septiembre de 2017.Stem cell activity must be strictly regulated to ensure a proper balance between proliferation and differentiation. This regulation is possible because stem cells reside in specific and restricted microenvironments called niches. The extra cellular matrix (ECM) is an essential component of these niches, where it provides structural support and facilitates proper signalling. For this reason, ECM remodelling in niches ought to be tightly regulated. Matrix metalloproteinases (MMPs), well-known ECM proteases, have been implicated in ECM metabolism in several tissues. MMP activity is generally controlled by Timp (tissue inhibitor of metalloproteinases) proteins. Studying the function of the only Drosophila timp gene in the female germline stem cell (GSC) niche, our laboratory has shown that timp mutant ovaries contain lower amounts of the structural ECM component Collagen IV and possess softer ECM than controls. Moreover, mutant ovaries display an aberrant organisation of the niche and show inefficient gamete production, phenotypes that could be linked to the increased MMP activity typical of timp ovaries. Interestingly, the reduction in gamete production is not due to GSC loss or to increased cell death. Instead, our in vivo analyses support the hypothesis that the reduced generation of germline cysts (and thus of female gametes) is a consequence of mutant GSCs taking longer to divide. In order to demonstrate a link between a prolonged cell cycle in timp mutant GSCs and tissue stiffness, we are studying in detail the cell cycle of control and timp mutant GSCs, with a focus on centrosome/centriole behaviour, spectrosome dynamics and mitosis.Peer Reviewe