What's new in edition 103 May 15th, 2026 Gene sites new with this edition

The Interactive Fly was first released July/August 1996, with updates provided at approximately one month intervals, through September 1997 (edition 13). Updating quarterly started with edition 14. With edition 40, the Interactive Fly began to schedule updates three times a year: fall, winter and spring. Starting with edition 101, full updates will be posted every 6 months.

Gene sites new with this edition of the Interactive Fly:

bourbon

In Drosophila ovaries, germ cells differentiate through several stages of cyst development before entering meiosis. This early differentiation program depends on both the stepwise deployment of specific regulatory mechanisms and on maintenance of germline sexual identity. The study of female sterile mutations that result in formation of germ cell tumors has been invaluable in identifying the mechanisms that control these developmental events. This study characterized the germ cell-enriched gene bourbon (bbn), null mutants of which cause the formation of a mixture of agametic ovarioles and cystic germ cell tumors. Proteomic analysis found Bbn forms a complex with Ovarian tumor (Otu), a protein previously linked with regulation of the sex determination factor Sex lethal (Sxl), and the Drosophila ortholog of c-Myc binding protein (Mycbp). Loss of Mycbp also results in the formation of cystic germ cell tumors. Bbn promotes the stability of Otu and fosters interactions between Otu and Mycbp. Germ cells from bbn and Mycbp mutants display a loss of Sxl expression specifically in the germline. Transgenic rescue experiments show the bbn sterile phenotype is independent from Sxl splicing defects. Further evidence suggests Otu physically interacts with and promotes Sxl protein stability. This function does not depend on Otu's deubiquitinase activity. Last, this study found the human orthologs of Otu and Mycbp, OTUD4, and MYCBP, also physically interact, suggesting conservation of function. Together these data provide insights into how a conserved complex promotes the germline expression of Sxl protein and the differentiation of Drosophila germ cells (Mercer, 2025).

Bub3 interacting GLEBS and Zinc finger domain protein

Exploring the role of phase separation in intracellular compartment formation is an active area of research. However, the associations of phase separation with intestinal stem cell (ISC)-dependent regeneration and aging remain unclear. This study demonstrates that BuGZ, a coacervating mitotic effector, shows age- and injury-associated condensation in Drosophila ISC nuclei during interphase. BuGZ condensation promotes ISC proliferation, affecting Drosophila gut repair and longevity. Moreover, m(6)A reader YT521-B acts as the transcriptional and functional downstream of BuGZ. The binding of YT521-B promotor or m(6)A writer Ime4/ Mettl14 to BuGZ controls its coacervation, indicating that the promotor may accelerate the phase transition of its binding transcription factor. Hence, it is proposed that phase separation and m(6)A regulators may be critical for ameliorating ISC-dependent gut regeneration and aging and requires further study (Zhang, 2023).

Cadherin 96Ca

Juvenile hormone (JH) is important to maintain insect larval status; however, its cell membrane receptor has not been identified. Using the lepidopteran insect Helicoverpa armigera (cotton bollworm), a serious agricultural pest, as a model, this study determined that receptor tyrosine kinases (RTKs) cadherin 96ca (CAD96CA), a protein with one n-terminal extracellular cadherin domain, and fibroblast growth factor receptor homologue (FGFR1) function as JH cell membrane receptors by their roles in JH-regulated gene expression, larval status maintaining, rapid intracellular calcium increase, phosphorylation of JH intracellular receptor MET1 and cofactor Taiman, and high affinity to JH III (see Juvenile Hormone III). Gene knockout of Cad96ca and Fgfr1 by CRISPR/Cas9 in embryo and knockdown in various insect cells, and overexpression of CAD96CA and FGFR1 in mammalian HEK-293T cells all supported CAD96CA and FGFR1 transmitting JH signal as JH cell membrane receptors (Li, 2025).

Dynactin 2, p50 subunit

Dynamitin (Dmn) is a major component of dynactin, a multiprotein complex playing important roles in a variety of intracellular motile events. Previous work has found that Wolbachia bacterial infection resulted in a reduction of Dmn protein. Since Wolbachia may modify sperm in male hosts, it was speculated that Dmn may have a function in male fertility. This study used nosGal4 to drive Dmn knock down in testes of Drosophila melanogaster to investigate the functions of Dmn in spermatogenesis. Knockdown of Dmn in testes dramatically decreased male fertility, overexpression of Dmn in Wolbachia-infected males significantly rescued male fertility, indicating an important role of Dmn in inducing male fertility defects following Wolbachia infection. Some scattered immature sperm with late canoe-shaped head distributed in the end of Dmn knockdown testis and only about half mature sperm were observed in the Dmn knockdown testis relative to those in the control. Transmission electron microscopy (TEM) exhibited fused spermatids in cysts and abnormal mitochondrial derivatives. Immunofluorescence staining showed significantly less abundance of tubulin around the nucleus of spermatid and scattered F-actin cones to different extents in the individualization complex (IC) during spermiogenesis in Dmn knockdown testes, which may disrupt the nuclear condensation and sperm individualization. Since dynein-dynactin complex has been shown to mediate transport of many cellular components, including mRNAs and organelles, these results suggest that Dmn may play an important role in Drosophila spermiogenesis by affecting transport of many important cytoplasmic materials (Wu, 2016).

identity crisis

H3K9me3-based gene silencing is a conserved strategy for securing cell fate, but the mechanisms controlling lineage-specific installation of this epigenetic mark remain unclear. In Drosophila, H3K9 methylation plays an essential role in securing female germ cell fate by silencing lineage inappropriate phf7 transcription. Thus, phf7 regulation in the female germline provides a powerful system to dissect the molecular mechanism underlying H3K9me3 deposition onto protein coding genes. Genetic studies were used to identify the essential cis-regulatory elements, finding that the sequences required for H3K9me3 deposition are conserved across Drosophila species. Transposable elements are also silenced by an H3K9me3-mediated mechanism. But the finding that phf7 regulation does not require the dedicated piRNA pathway components, piwi, aub, rhino, panx, and nxf2, indicates that the mechanisms of H3K9me3 recruitment are distinct. Lastly, it was discovered that an uncharacterized member of the zinc finger associated domain (ZAD) containing C2H2 zinc finger protein family, IDENTITY CRISIS (IDC; CG4936), is necessary for H3K9me3 deposition onto phf7. Loss of idc in germ cells interferes with phf7 transcriptional regulation and H3K9me3 deposition, resulting in ectopic PHF7 protein expression. IDC's role is likely to be direct, as it localizes to a conserved domain within the phf7 gene. Collectively, these findings support a model in which IDC guides sequence-specific establishment of an H3K9me3 mini domain, thereby preventing accidental female-to-male programming (Shapiro-Kulnane, 2022).

pallidin

The Pallidin protein is a central subunit of a multimeric complex called biogenesis of lysosome-related organelles complex 1 (BLOC1) that regulates specific endosomal functions and has been linked to schizophrenia. Downregulation of Pallidin and other members of BLOC1 in the surface glia, the Drosophila equivalent of the blood-brain barrier, reduces and delays nighttime sleep in a circadian-clock-dependent manner. In agreement with BLOC1 involvement in amino acid transport, downregulation of the large neutral amino acid transporter 1 (LAT1)-like transporters JhI-21 and mnd, as well as of TOR (target of rapamycin) amino acid signaling, phenocopy Pallidin knockdown. Furthermore, supplementing food with leucine normalizes the sleep/wake phenotypes of Pallidin downregulation, and this study identified a role for Pallidin in the subcellular trafficking of JhI-21. Finally, evidence is provided that Pallidin in surface glia is required for GABAergic neuronal activity. These data identify a BLOC1 function linking essential amino acid availability and GABAergic sleep/wake regulation (Li, 2023).

papilin

Differentiation of prohaemocytes, the precursors of Drosophila blood cells (haemocytes), and the release of haemocytes from the lymph gland, a major larval haematopoietic organ, are vital responses to wasp infestation or tissue degeneration. Although cells and extracellular matrix (ECM) in the lymph gland are known to play a crucial role in haemocyte differentiation, the underlying mechanisms remain unclear. This study shows that the matrix glycoprotein papilin (Ppn) is essential for maintaining the prohaemocyte population in lymph glands. In Ppn-depleted larvae, haemocyte differentiation increased with a reduction in the prohaemocyte-containing medullary zone, and lymph gland lobes dispersed prematurely. Ppn was synthesised by plasmatocytes, forming lamellae mainly in the medullary zone. Microbial infection or wasp infestation disrupted the Ppn meshwork within lymph glands. Ppn colocalised with collagen, laminin, nidogen and perlecan. Ppn depletion disrupted the ECM structure, including perlecan organisation. Phenotypes caused by Ppn depletion were partially rescued by perlecan overexpression or inactivation of the epidermal growth factor receptor pathway. Thus, Ppn is crucial for maintaining lymph gland architecture and regulating haemocyte differentiation, highlighting an intricate interaction between the ECM and signalling pathways in haematopoiesis (Lee, 2025).

Ras association domain family member 8 (Rasf8)

Collective cell migration is a key driver of tissue morphogenesis and cancer invasion. This study identified the tumor suppressor Ras association domain-containing protein 8 (RASSF8) as a WAVE interactor required for border cell migration. RASSF8 colocalizes with F-actin and cell adhesion molecules at border cell- border cell contacts. Loss of RASSF8 function results in border cell cohesion defects, a phenotype associated with changes in the localization of the Echinoid (Ed) and Coracle (Cora). Cell-type-specific RNA interference (RNAi) experiments suggest that cohesion defects are caused by changes in localization of Ed rather than E-cadherin. Gain-of-function experiments further revealed reciprocal functional interactions between RASSF8 and WAVE controlling collective border cell movement. Thus, a dual function is proposed of RASSF8 in coordinating border cell cluster behavior. RASSF8 is thought to regulate the collective movement of border cells by restricting WAVE function, while it controls the epithelial cluster integrity by regulating cell-cell adhesion and septate junction molecules such as Ed and Cora (Hohne, 2025).

shriveled

In the nervous system, reliable communication depends on the ability of neurons to adaptively remodel their synaptic structure and function in response to changes in neuronal activity. While neurons are the main drivers of synaptic plasticity, glial cells are increasingly recognized for their roles as active modulators. However, the underlying molecular mechanisms remain unclear. In this study, using Drosophila neuromuscular junction as a model system for a tripartite synapse, this study showed that peripheral glial cells collaborate with neurons at the NMJ to regulate activity-induced synaptic remodeling, in part through a protein called Shriveled (Shv). shv is an activator of integrin signaling previously shown to be released by neurons during intense stimulation at the fly NMJ to regulate activity-induced synaptic remodeling. This study demonstrate that Shv is also present in peripheral glia, and glial shv is both necessary and sufficient for synaptic remodeling. However, unlike neuronal shv, glial shv does not activate integrin signaling at the NMJ. Instead, it regulates synaptic plasticity in two ways: 1) maintaining the extracellular balance of neuronal shv proteins to regulate integrin signaling, and 2) controlling ambient extracellular glutamate concentration to regulate postsynaptic glutamate receptor abundance. Loss of glial cells showed the same phenotype as loss of shv in glia. Together, these results reveal that neurons and glial cells homeostatically regulate extracellular shv protein levels to control activity-induced synaptic remodeling. Additionally, peripheral glia maintains postsynaptic glutamate receptor abundance and contribute to activity-induced synaptic remodeling by regulating ambient glutamate concentration at the fly NMJ (Chang, 2025).

Soul

The prothoracic gland (PG) is a major insect endocrine organ. It is the principal source of insect steroid hormones, and critical for key developmental events such as the molts, the establishment of critical weight (CW), pupation, and sexual maturation. However, little is known about the developmental processes that regulate PG morphology. This study identified soul, which encodes a PG-specific basic helix-loop-helix (bHLH) transcription factor. Tap, also a bHLH protein, dimerizes with Soul. Both are expressed in the developing PG. Interfering with either soul or tap function caused strikingly similar phenotypes, resulting in small and fragmented PGs, the abolishment of steroid hormone-producing gene expression, larval arrest, and a failure to undergo metamorphosis. Furthermore, both soul and tap showed expression peaks just prior to the CW checkpoint. Disrupting soul- or tap-function before, but not after, the CW checkpoint caused larval arrest, and perturbed highly similar gene cohorts, which were enriched for regulators and components of the steroid hormone biosynthesis pathway. Intriguingly, a chitin-based cuticle gene, Cpr49Ah, and a POU domain transcription factor gene, pdm3, are direct target genes of the Soul/Tap complex, and disruption of either phenocopied key aspects of soul/tap loss-of-function phenotypes. Taken together, these findings demonstrate that the Soul/Tap heterodimer resides at the top of a complex gene hierarchy that drives PG development, CW establishment, and steroid hormone production (liu, 2024).

Ubiquitin-specific protease 7

Meiosis is a form of cell division that is essential to sexually reproducing organisms and is therefore highly regulated. Each event of meiosis must occur at the correct developmental stage to ensure that chromosomes are segregated properly during both meiotic divisions. One unique meiosis-specific structure that is tightly regulated in terms of timing of assembly and disassembly is the complex (SC). While the mechanism(s) for assembly and disassembly of the SC are poorly understood in Drosophila melanogaster, posttranslational modifications, including ubiquitination and phosphorylation, are known to play a role. This study identified a role for the deubiquitinase Ubiquitin-specific protease 7 Usp7 in the maintenance of the SC in early prophase and shows that its function in SC maintenance is independent of the meiotic recombination process. Using two usp7 shRNA constructs that result in different knockdown levels, this study has shown that the presence of SC through early/mid-pachytene is critical for normal levels and placement of crossovers (Lake, 2024).

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