Biology subjects

Fabian, L.

Publications and source records attributed to Fabian, L..

4 recordsLinked to original sources

bioRxiv2026

A genetic screen to identify novel interactions of the phosphatidylinositol phosphate signaling pathway in Drosophila spermatogenesis

Phosphatidylinositol (PI) phosphates (PIPs) are membrane lipids with crucial roles in intracellular signaling, membrane trafficking and cytoskeletal organization. To perturb PIP function in Drosophila melanogaster sperm development, we previously expressed the Salmonella PIP phosphatase SigD (also known as SopB) under control of a spermatocyte- specific promoter. SigD expression results in reduced levels of plasma membrane PI 4,5-bisphosphate [PI(4,5)P2; henceforth PIP2] and male sterility. Transgenic lines expressing high levels of SigD (SigD-high) exhibit defects in spermatocyte cytokinesis, ciliary transition zone maturation and spermatid elongation, whereas lines expressing low levels of SigD (SigD-low) have defects in nuclear shaping and spermatid cell polarization. To further investigate the role of PIPs during Drosophila sperm development, we conducted a sensitized genetic screen to identify suppressors and enhancers of SigD-low phenotypes. From a screen of 760 chromosomal deficiencies spanning 83.6% of chromosomes 2 and 3, we identified 80 interacting regions that were further narrowed down to 40 individual suppressors. Among the strongest interactors were genes involved in microtubule dynamics, nucleocytoplasmic transport and membrane trafficking. The novel genetic interactions identified by our screen pave the way for further investigation into molecular mechanisms underlying the affected aspects of sperm development.

genetics↗

bioRxiv2026

A shared functional organisation underlies vascular disease remodelling

Cardiovascular disease involves coordinated remodelling across multiple biological processes. Gene-level signatures vary substantially between studies because different combinations of genes can support similar biological processes. Pathway-level analyses can provide more stable representations of these processes but typically consider pathways independently. We hypothesised that grouping related pathways into conserved biological functions and quantifying their relative weighting would reveal a higher-order, transferable property of vascular tissue that we term functional organisation. We quantified the relative weighting of six conserved biological functions across independent transcriptomic datasets spanning human vascular disease, experimental models and therapeutic interventions. Vascular tissues exhibited a reproducible functional organisation defined by the balance of these functions. A dominant remodelling trajectory captured coordinated, nonlinear rebalancing of structural, immune, signalling and metabolic programmes, while a second dimension distinguished contractile/ECM organisation from immune activity. This organisation was preserved across independently reconstructed reference cohorts and remained robust to analytical sensitivity testing. When independent datasets were projected into this fixed framework, biological and clinical phenotypes occupied coherent positions along the remodelling landscape. Plaque-derived vascular, stromal and immune cell populations also occupied ordered functional positions, linking cellular heterogeneity to tissue-level organisation. The same organisational structure generalised across atherosclerosis, peripheral vascular disease and abdominal aortic aneurysm and revealed continuous biological heterogeneity within conventional clinical classifications. Genetic, pharmacological and dietary perturbations reproducibly shifted functional organisation, demonstrating that organisational state is dynamic and biologically responsive. Together, these findings identify functional organisation as a reproducible tissue-level property of vascular remodelling and provide a framework for understanding cardiovascular disease as coordinated rebalancing of biological functions rather than alteration of individual pathways in isolation.

bioinformatics↗

bioRxiv2020

De Novo Phosphoinositide Synthesis in Zebrafish Is Required for Triad Formation but Not Essential for Myogenesis

Phosphoinositides (PIPs) and their regulatory enzymes are key players in many cellular processes and are required for aspects of vertebrate development. Dysregulated PIP metabolism has been implicated in several human diseases, including a subset of skeletal myopathies that feature structural defects in the triad. The role of PIPs in skeletal muscle formation, and particularly triad biogenesis, has yet to be determined. CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) catalyzes the formation of phosphatidylinositol, which is the base of all PIP species. Loss of CDIPT should, in theory, result in the failure to produce PIPs, and thus provide a strategy for establishing the requirement for PIPs during embryogenesis. In this study, we generated cdipt mutant zebrafish and determined the impact on skeletal myogenesis. Analysis of cdipt mutant muscle revealed no apparent global effect on early muscle development. However, small but significant defects were observed in triad size, with T-tubule area, inter terminal cisternae distance and gap width being smaller in cdipt mutants. This was associated with a decrease in motor performance. Overall, these data suggest that myogenesis in zebrafish does not require de novo PIP synthesis but does implicate a role for CDIPT in triad formation.

developmental biology↗

bioRxiv2018

Phosphatidylinositol 4,5-bisphosphate regulates cilium transition zone maturation in Drosophila melanogaster

Cilia are cellular antennae that are essential for human development and physiology. A large number of genetic disorders linked to cilium dysfunction are associated with proteins that localize to the ciliary transition zone (TZ), a structure at the base of cilia that regulates trafficking in and out of the cilium. Despite substantial effort to identify TZ proteins and their roles in cilium assembly and function, processes underlying maturation of TZs are not well understood. Here, we report a role for the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) in TZ maturation in the Drosophila melanogaster male germline. We show that reduction of cellular PIP2 levels by ectopic expression of a phosphoinositide phosphatase or mutation of the type I phosphatidylinositol phosphate kinase Skittles induces formation of longer than normal TZs. These hyperelongated TZs exhibit functional defects, including loss of plasma membrane tethering. We also report that the onion rings (onr) allele of Drosophila exo84 decouples TZ hyperelongation from loss of cilium-plasma membrane tethering. Our results reveal a requirement for PIP2 in supporting ciliogenesis by promoting proper TZ maturation.\n\nBrief summary statementThe authors show that the membrane phospholipid PIP2, and the kinase that produces PIP2 called Skittles, are needed for normal ciliary transition zone morphology and function in the Drosophila male germline.

cell biology↗