stall Encodes an ADAMTS Metalloprotease and Interacts Genetically With Delta in Drosophila Ovarian Follicle Formation

Abstract

Ovarian follicle formation in Drosophila melanogaster requires stall (stl) gene function, both within and outside the ovary, for follicle individualization, stalk cell intercalation, and oocyte localization. We have identified the stl transcript as CG3622 and confirmed the presence of three alternatively spliced isoforms, contrary to current genome annotation. Here we show that the gene is expressed in both ovarian and brain tissues, which is consistent with previous evidence of an ovary nonautonomous function. On the basis of amino acid sequence, stl encodes a metalloprotease similar to the ''a disintegrin and metalloprotease with thrombospondin'' (ADAMTS) family. Although stl mutant ovaries fail to maintain the branched structure of the fusome and periodically show improperly localized oocytes, stl mutants do not alter oocyte determination. Within the ovary, stl is expressed in pupal basal stalks and in adult somatic cells of the posterior germarium and the follicular poles. Genetically, stl exhibits a strong mutant interaction with Delta (Dl), and Dl mutant ovaries show altered stl expression patterns. Additionally, a previously described genetic interactor, daughterless, also modulates stl expression in the somatic ovary and may do so directly in its capacity as a basic helix-loop-helix (bHLH) transcription factor. We propose a complex model of long-range extraovarian signaling through secretion or extracellular domain shedding, together with local intraovarian protein modification, to explain the dual sites of Stl metalloprotease function in oogenesis.

Sol narae (Sona) is a Drosophila ADAMTS involved in Wg signaling

“…Drosophila has six ADAMTSs: Stall, Papilin, CG4096, CG6232, ADAMTS-A and CG9850 (Sona) 32 33 34 35 . Sona described in this study is Sona-PA, one of five Sona isoforms described in Flybase.…”

“…ADAMTSs are secreted metalloproteases that are known to be involved in mainly ECM remodeling. Among six ADAMTSs in the fly, Papilin is essential for the formation of basement membrane and fly development 32 , Stall functions in ovarian follicle formation and exhibits positive genetic interaction with Delta 35 , and ADAMTS-A is important for cell migration, especially in detaching cells from the apical ECM in salivary gland 34 . In this report, we have shown that Sona is a fly ADAMTS essential for fly development and survival.…”

New Negative Feedback Regulators of Egfr Signaling inDrosophila

“…It is one of 3 genes in Drosophila belonging to the ADAMTS family ( Figure 6) (Nicholson et al 2005). Only one of these, stall, has been analyzed genetically and found to be involved in ovary development (Ozdowski et al 2009 Sequence analysis places CG4096 closest to human ADAMTS7 and ADAMTS12 (Nicholson et al 2005). But CG4096 does not possess a protease and a lacunin (PLAC) domain or a mucin domain, which are seen in mammalian genes ( Figure 6) (Porter et al 2005;Apte 2009).…”

Characterizing the genetic basis of copper toxicity inDrosophilareveals a complex pattern of allelic, regulatory, and behavioral variation

“…In addition 538 to these copper-associated genes, we observed 64 genes with functions related to homeostasis 539 or detoxification of zinc, 2 genes involved with manganese regulation, and 19 genes involved in 540 binding unspecified metals. Of particular interest among these genes are Catsup (Q3), ZnT41F 541 (Q4), and stl (Q7), which are all associated with zinc transport or detoxification (Yepiskoposyan 542 et al 2006;Ozdowski et al 2009;Lye et al 2013;Navarro and Schneuwly 2017), trpl (Q5) and 543 DCP2 (Q8), which are hypothesized to be involved in manganese ion binding (Thurmond et al 544 2019), and swm (Q3), babo (Q5), and whd (Q5), which are thought to be involved in binding of 545 unspecified metal ions based on gene ontology prediction (Gaudet et al 2011;Thurmond et al 546 2019). 547…”