br Material and methods br Introduction

Material and methods
Introduction The stem cell niche concept was first proposed more than three decades ago for the human hematopoietic system (Lin, 2002). In the following the stem cell niche concept has also been proposed for several other tissues including the epidermis, the intestinal epithelium, the neural system (Shepherd and Bate, 1990; Taghert et al., 1984; Doe et al., 1985; Doe and Goodman, 1985), and the gonads (Lin, 2002). Insect model systems of the neural stem cell niche have in many respects marked the beginning in developing deeper insights into the niche–stem cell relationship. In this report we focus on the interaction between male germline stem glucose transport proteins (GSCs) and supporting somatic elements, the apical cells (ACs), now known as their niche (Lin, 2002). Early investigators marveled at the intricate morphological interrelations observed in light microscopical preparations of lepidopteron male germinal proliferation centers, the apical complexes of testicular follicles (for review, see Roosen-Runge, 1977). They proposed a regulatory function of ACs by interactions with GSCs, whereas the traditional view of subsequent investigators favored a nutritive role of ACs for the developing spermatogonia (for reviews, see Schmidt and Dorn, 2004; Schmidt et al., 2001). The study of Szöllösi and Marcaillou (1979) on the fine structure of the AC in Locusta migratoria sparked new interest on this extraordinary cell and its function. Szöllösi and Marcaillou observed large amounts of smooth endoplasmic reticulum in the AC which prompted them to speculate that the cell may synthesize a lipid, presumably juvenile hormone that regulates spermatogenesis. Smooth endoplasmic reticulum is also prominent in the ACs of the lepidopteran Euproctis chrysorrhea (Leclercq-Smekens, 1978). In this case, the authors suspected the production and secretion of a steroid that affects spermatogenesis. None of these speculations have been verified. Recently, the apical complex of Drosophila melanogaster has emerged as a successful model for the revelation of signaling interactions between GSCs and their niche, the ACs (lately called hub cells in Drosophila), and the cyst progenitor cells (CPCs) as well. According to these studies (for reviews, see Li and Xie, 2005; Xie et al., 2005), the niche interacts with GSCs in several ways: it regulates GSC self-renewal and proliferation, it upholds the stemness of GSCs, and it is probably necessary for the survival of GSCs (Zahn et al., 2007). GSCs apparently also have an effect on their niche, which is indicated by the observation that hub cells reenter the cell cycle in agametic testes (Gonczy and DiNardo, 1996). Generally, insect ACs do not divide during postembryonic development (Schmidt et al., 2001). The Drosophila model played a crucial role for the establishment of the stem cell–niche theory for an array of tissues ranging from the neural system to the gonads (Lin, 2002). This theory probably applies to all embryonic and postembryonic/adult stem cells of animal and human regenerative tissues (Lin, 2002). A disturbance of the stem cell–niche relationship supposedly causes severe diseases and is therefore the subject of intense research (Reya and Clevers, 2005; Scadden, 2006). In order to maintain tissue homeostasis, it is imperative that death of exhausted or injured differentiated cells is exactly matched by the differentiation of replacing cells generated by stem cells. Stem cell divisions can occur in one of two ways: they can be either symmetric, resulting in two differentiated daughter cells, or asymmetric, resulting in a stem cell (stem cell self-renewal) and a progenitor cell that eventually starts differentiation and replaces a lost tissue cell (Doe, 2008; Morrison and Kimble, 2006; Yamashita et al., 2003, 2007). Signals from the niche are thought to play a decisive role in the decision whether symmetric or asymmetric division takes place and at which rate. A malfunction of the niche could result in either an overproduction of stem cells and/or progenitor cells, leading to tumorigenesis, or a shortage of progenitor cells resulting in tissue disintegration (Holtmann and Dorn, 2009).