Article

Lasp anchors the Drosophila male stem cell niche and mediates spermatid individualization

Department of Biology, McGill University, 1205 Dr. Penfield Avenue, Montreal, QC, Canada H3A 1B1.
Mechanisms of development (Impact Factor: 2.44). 09/2008; 125(9-10):768-76. DOI: 10.1016/j.mod.2008.06.012
Source: PubMed

ABSTRACT

Lasp family proteins contain an amino-terminal LIM domain, two actin-binding nebulin repeats and a carboxyl-terminal SH3 domain. Vertebrate Lasp-1 localizes to focal adhesions and the leading edge of migrating cells, and is required for cell migration. To assess the in vivo function of Lasp, we generated a null mutant in Drosophila Lasp. Lasp(1) is homozygous viable, but male sterile. In Lasp mutants the stem cell niche is no longer anchored to the apical tip of the testis, and actin cone migration is perturbed resulting in improper spermatid individualization. Hub cell mislocalization can by phenocopied by expressing Lasp or betaPS integrin RNAi transgenes in somatic cells, and Lasp genetically interacts with betaPS integrin, demonstrating that Lasp functions together with integrins in hub cells to anchor the stem cell niche. Finally, we show that the stem cell niche is maintained even if it is not properly localized.

Download full-text

Full-text

Available from: Frieder Schöck, Dec 24, 2013
  • Source
    • "It becomes obvious that proper niche function needs to be actively maintained in order to avoid the accumulation of cell autonomous and non-autonomous effects in the Drosophila testis (Kitadate et al., 2007; Le Bras and Van Doren, 2006; Lee et al., 2008; Papagiannouli et al., 2014; Tanentzapf et al., 2007). The employment of a combination of critical players and pathways that continuously provide inputs to secure Fig. 7. Schematic diagram of genetic interactions among the key players involved in larval male niche positioning. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A fundamental question is how complex structures are maintained after their initial specification. Stem cells reside in a specialized microenvironment, called niche, which provides essential signals controlling stem cell behavior. We addressed this question by studying the Drosophila male stem cell niche, called the hub. Once specified, the hub cells need to maintain their position and architectural integrity through embryonic, larval and pupal stages of testis organogenesis and during adult life. The Hox gene Abd-B, in addition to its described role in male embryonic gonads, maintains the architecture and positioning of the larval hub from the germline by affecting integrin localization in the neighboring somatic cyst cells. We find that the AbdB-Boss/Sev cascade affects integrin independent of Talin, while genetic interactions depict integrin as the central downstream player in this system. Focal adhesion and integrin-adaptor proteins within the somatic stem cells and cyst cells, such as Paxillin, Pinch and Vav, also contribute to proper hub integrity and positioning. During adult stages, hub positioning is controlled by Abd-B activity in the outer acto-myosin sheath, while Abd-B expression in adult spermatocytes exerts no effect on hub positioning and integrin localization. Our data point at a cell- and stage-specific function of Abd-B and suggest that the occurrence of new cell types and cell interactions in the course of testis organogenesis made it necessary to adapt the whole system by reusing the same players for male stem cell niche positioning and integrity in an alternative manner. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Jul 2015 · Mechanisms of development
  • Source
    • "RightsLink service; License Number: 3511390160410). (C) The players that control hub positioning and integrity in embryonic (left column), larval (middle column) and adult (right column) stages are shown: Integrin (Lee et al., 2008; Tanentzapf et al., 2007), Talin (Tanentzapf et al., 2007) and Sev (Kitadate et al., 2007; Papagiannouli et al., 2014) are required in the somatic linage (highlighted in green) and Boss (Kitadate et al., 2007; Papagiannouli et al., 2014 "
    [Show abstract] [Hide abstract]
    ABSTRACT: A fundamental question in biology is how complex structures are maintained after their initial specification. We address this question by reviewing the role of the Hox gene Abd-B in Drosophila testis organogenesis, which proceeds through embryonic, larval and pupal stages to reach maturation in adult stages. The data presented in this review highlight a cell- and stage-specific function of Abd-B, since the mechanisms regulating stem cell niche positioning and architecture at different stages seem to be different despite the employment of similar factors. In addition to its described role in the male embryonic gonads, sustained activity of Abd-B in the pre-meiotic germline spermatocytes during larval stages is required to maintain the architecture of the stem cell niche by regulating βPS-Integrin localization in the neighboring somatic cyst cells. Loss of Abd-B is associated with cell non-autonomous effects within the niche, leading to a dramatic reduction of pre-meiotic cell populations in adult testes. Identification of Abd-B target genes revealed that Abd-B mediates its effects by controlling the activity of the Sevenless ligand Boss via its direct targets Src42A and Sec63. During adult stages, when testis morphogenesis is completed with the addition of the acto-myosin sheath originating from the genital disc, stem cell niche positioning and integrity is regulated by Abd-B activity in the acto-myosin sheath whereas Integrin acts in an Abd-B independent way. It seems that the occurrence of new cell types and cell interactions in the course of testis organogenesis made it necessary to adapt the system to the new cellular conditions by reusing the same players for testis stem cell niche positioning in an alternative manner.
    Full-text · Article · Jan 2015 · Computational and Structural Biotechnology Journal
  • Source
    • "Integrin signaling has a permissive role for ISC proliferation induced by local proliferative signals Previous studies have shown that ISC proliferation in the Drosophila midgut can be regulated by Wg and JAK/STAT and EGFR signaling pathway activities (Beebe et al., 2010; Biteau and Jasper, 2011; Buchon et al., 2010; Jiang et al., 2011; Lee et al., 2009; Lin et al., 2008, 2010; Xu et al., 2011). We therefore tested whether forced activation of these signaling pathways could promote ISC proliferation when integrin is depleted. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tissue-specific stem cells are maintained by both local secreted signals and cell adhesion molecules that position the stem cells in the niche microenvironment. In the Drosophila midgut, multipotent intestinal stem cells (ISCs) are located basally along a thin layer of basement membrane that composed of extracellular matrix (ECM), which separates ISCs from the surrounding visceral musculature: the muscle cells constitute a regulatory niche for ISCs by producing multiple secreted signals that directly regulate ISC maintenance and proliferation. Here we show that integrin-mediated cell adhesion, which connects the ECM and intracellular cytoskeleton, is required for ISC anchorage to the basement membrane. Specifically, the α-integrin subunits including αPS1 encoded by mew and αPS3 encoded by scb, and the β-integrin subunit encoded by mys are richly expressed in ISCs and are required for the maintenance, rather than their survival or multiple lineage differentiation. Furthermore, ISC maintenance also requires the intercellular and intracellular integrin signaling components including Talin, Integrin-linked kinase (Ilk), and the ligand, Laminin A. Notably, integrin mutant ISCs are also less proliferative, and genetic interaction studies suggest that proper integrin signaling is a pre-requisite for ISC proliferation in response to various proliferative signals and for the initiation of intestinal hyperplasia after loss of adenomatous polyposis coli (Apc). Our studies suggest that integrin not only functions to anchor ISCs to the basement membrane, but also serves as an essential element for ISC proliferation during normal homeostasis and in response to oncogenic mutations.
    Full-text · Article · Feb 2013 · Developmental Biology
Show more