Biology subjects

Eckardt, F.

Publications and source records attributed to Eckardt, F..

3 recordsLinked to original sources

bioRxiv2026

Genetic interaction approaches reveal emerging roles of innexins in development : Insights from a novel pannier–innexin-2 interaction during Drosophila embryogenesis

Effective communication between cells is essential for the typical development and behaviour of an organism. In this context, gap junctions represent the most universally preserved components at cellular membranes of multicellular organisms, facilitating metabolic and electrical connections between cells. Disruptions in these junctions have been linked to various developmental abnormalities and pathological conditions in humans. The invertebrate gap junction proteins, referred to as innexins, exhibit conserved cellular and molecular mechanisms of functioning with their vertebrate counterparts, known as connexins. Consequently, they provide valuable means for studying and understanding the functions of gap junctions in development. In the Drosophila embryo, innexin-2 is expressed in the amnioserosa and ectoderm, where it is required for epithelial morphogenesis. Genetic depletion of innexin-2 results in cuticular defects and embryonic lethality. Pannier, a GATA family transcription factor, is a key regulator of dorsal tissue development in Drosophila and is expressed in the amnioserosa, dorsal ectoderm and the dorsal vessel during embryogenesis. Pannier mutants exhibit defects in dorsal closure, cuticle formation, and cardiac specification. Although substantial evidence from vertebrate systems indicate that connexin expression is regulated by transcription factors such as GATA4, Nkx2.5, Tbx2, Tbx3, and Tbx5, whether a similar regulatory relationship exists between these transcription factors and gap junction proteins in Drosophila remains unknown. In this study, we investigate how innexin mediated intercellular communication impacts pannier dependent morphogenetic processes during Drosophila embryogenesis.

Developmental Biology↗

bioRxiv2025

Spatial Expression Pattern and Cellular Organisation of Gap Junctions in Third Instar Wing Imaginal Discs of Drosophila melanogaster

The Drosophila wing imaginal disc serves as a powerful model to study intercellular communication during development. In our study, we report and discuss the expression pattern and cellular distribution of innexin-1, innexin-2 and innexin-3 in the cells of the wing imaginal discs. Our immunohistochemical data show that all three innexins are broadly expressed across the membranes of both the disc proper and peripodial epithelial cells of the wing disc. The stainings further reveal that, within the disc proper epithelium, junctional proteins are arranged in a clear apico-basal hierarchy: cadherins at the apical surface, followed by septate junction proteins, with innexins localised sub-apically beneath these components. All three innexins are enriched within this sub-apical domain, and are additionally detected at mid-and baso-lateral sites in varying levels. Notably, innexin-2 exhibits partial colocalization with coracle, a septate junction-associated protein, suggesting a functional association. In the peripodial epithelium, innexins are detected in distinct punctate patterns across cell membranes, implying heterogeneity in their molecular characteristics. To validate these expression patterns, we carried out tissue-specific RNAi-mediated knockdowns using the pannier-Gal4 driver targeting the notum, a structurally and functionally important but underexplored region in innexin research. Knockdown of innexin-2 and innexin-3 led to complete loss of their expression within this region. Notably, silencing of innexin-2 also affected the expression of septate junction associated proteins and innexin-3 knockdown was accompanied by a significant reduction in disc size and altered morphology. These findings depict and confirm the presence of innexins in the notum region and also indicate that individual innexins may have distinct or shared functional roles within the same tissue domain of expression. Their localization to specific membrane domains is likely to underlie their differential modes of action. Although previous studies have demonstrated the functional involvement of gap junctions in various aspects of normal wing development in Drosophila, a description of the arrangement of innexins on the third instar wing discs is required for better understanding of their roles. Our study addresses this gap by providing a comprehensive analysis of the cellular localisation and organisation of gap junctions, specifically innexin-1,-2 and-3, within the third instar wing discs, thereby supporting and extending existing knowledge.

cell biology↗

bioRxiv2025

Targeting the homeodomain of ceramide-synthase can ameliorate insulin resistance

Multiple studies have linked ceramide accumulation with insulin resistance and diabetes. Ceramide Synthases (CerS) are at the center of ceramide de novo formation. Impaired CerS activity leads to lower ceramide and resolves insulin resistance. Drosophila has only one CerS, named Schlank, which contains a catalytic lag1p motif and, like many CerS, a homeodomain regulating lipid homeostasis. How CerS homeodomains are associated with diabetes has been little studied. Here we demonstrate that, depending on the respective mutation in the CerS homeodomain high sugar diet (HSD)-induced insulin resistance is exacerbated or ameliorated. HSD shifts the profile of sphingolipids towards polyunsaturated longer sphingoid bases, systemic insulin signaling is reduced, as indicated by nuclear accumulation of FoxO, and secretion of insulin-like peptide 2 (DILP2) is impaired. Expression of a CerS variant with a mutation in the nuclear localization signal 2 within its homeodomain in the fat body improves systemic insulin signaling and DILP2 release. Thus, the CerS homeodomain may be a potential target to attenuate insulin resistance.

genetics↗