Biology subjects

Preussner, M.

Publications and source records attributed to Preussner, M..

6 recordsLinked to original sources

bioRxiv2026

Shroom3-dependent pillar cell constriction establishes a mechanical threshold for respiratory lamellar stability

How developing organs acquire complex architectures while maintaining tissue integrity under mechanical stress is a fundamental question in mechanobiology. In the gill, pillar cells support the thin respiratory lamellae, but how they withstand hemodynamic forces is unknown. Here, we show that actomyosin-rich contractile apparatuses (CA) in zebrafish pillar cells act as load-bearing units that generate contractile forces and stabilize the lamellae through adhesion to and enclosure of extracellular collagen columns. CA number correlates with pillar cell constriction, linking subcellular architecture to tissue geometry. We further identify Shroom3 and Vinculin b as key regulators of CA assembly and force transmission: shroom3 deficiency or loss of vclb impairs CA formation and reduces pillar cell constriction, while loss of shroom3 causes lamellar collapse. Together, these findings support a mechanical threshold model in which lamellar integrity depends on a minimum number of CAs per pillar cell and establish the gill lamellae as a model for linking subcellular contractility to tissue-scale mechanical stability.

developmental biology↗

bioRxiv2025

Lifelong development of zebrafish gills: Asymmetries in early vascular patterning predict adult gill architecture

Gills are essential for fish respiration and have a highly specialized cellular architecture enabling efficient gas exchange. Surprisingly, the developmental processes underlying gill formation in zebrafish remain poorly understood. Here, we present for the first time a comprehensive analysis of the morphogenesis of gill arteries, filaments and lamellae during lifelong development. Our results provide important insights into the temporal and spatial pattern of gill angiogenesis, revealing fundamental differences in the formation of lateral versus medial filaments along the dorso-ventral axis. These early asymmetries correlate with, and likely underlie, the structural asymmetries observed in adult gills, which we quantitatively characterize. This indicates that a region-specific developmental programme establishes a blueprint for gill architecture maintained throughout life. We further show that lamellae develop through a complex interplay between endothelial and cranial neural crest-derived pillar cells. Notably, lamellar size, which strongly influences respiratory efficiency, depends on the position of the filament in the arch. Together, our work identifies key cellular and temporal mechanisms driving gill development and provides a framework to investigate broader principles of branching morphogenesis and angiogenesis in vertebrates.

developmental biology↗

bioRxiv2023

Identification of a link between splicing and endoplasmic reticulum proteostasis

The role of general splicing in endoplasmic reticulum (ER)-proteostasis remains poorly understood. Here, we identify SNRPB, a component of the spliceosome, as a novel regulator of export from the ER. Mechanistically, SNRPB regulates the splicing of components of the ER export machinery, including Sec16A, a regulator of ER exit sites. Loss of function of SNRPB is causally linked to cerebro-costo-mandibular syndrome (CCMS), a genetic disease characterized by bone defects. We show that heterozygous deletion of SNRPB in mice resulted in intracellular accumulation of type-1 collagen as well as bone defects reminiscent of CCMS. Silencing SNRPB inhibited osteogenesis in vitro, which could be rescued by overexpression of Sec16A. This indicates that the role of SNRPB in osteogenesis is linked to its effects on ER export. Finally, we show that SNRPB is a target for the unfolded protein response (UPR), which supports a mechanistic link between the spliceosome and ER-proteostasis. Our work highlights SNRPB as a novel node in the proteostasis network, shedding light on CCMS pathophysiology.

cell biology↗

bioRxiv2022

ASO targeting temperature-controlled RBM3 poison exon splicing prevents neurodegeneration in vivo

Neurodegenerative diseases are increasingly prevalent in the aging population, yet currently no disease-modifying treatments are available. Increasing the expression of the cold-shock protein, RBM3, through therapeutic hypothermia is remarkably neuroprotective, but cooling poses a health risk itself, strongly limiting its clinical application. Selective upregulation of RBM3 at normothermia thus holds immense therapeutic potential. Here we identify a poison exon within the RBM3 gene that is solely responsible for cold-induced RBM3 expression. Genetic removal or ASO-mediated manipulation of this exon yields high RBM3 levels independent of cooling. Notably, a single administration of ASO to exclude the poison exon, using FDA-approved chemistry, results in long-lasting increase of RBM3 expression in mouse brains. In prion-diseased mice, this treatment leads to remarkable neuroprotection, with prevention of neuronal loss and spongiosis despite high levels of prion protein. RBM3-inducing ASOs could thus broadly deliver protection in humans in conditions ranging from acute brain injury to Alzheimers disease. One sentence summaryInducing cold shock protein RBM3 by modulating its alternative splicing at normothermia is neuroprotective in vivo

molecular biology↗

bioRxiv2022

Branch point evolution controls species-specific alternative splicing and regulates long term potentiation

Regulation and functionality of species-specific alternative splicing has remained enigmatic to the present date. Calcium/calmodulin-dependent protein kinase II{beta} (CaMKII{beta}) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific Camk2{beta} alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strengths during evolution globally renders constitutive exons alternative, thus providing a paradigm for cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9 we introduced a weaker human branch point into the mouse genome, resulting in human-like CAMK2B splicing in the brain of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point-controlled, species-specific alternative splicing with a fundamental function in learning and memory.

molecular biology↗

bioRxiv2020

Alternative splicing coupled nonsense-mediated decay shapes the temperature-dependent transcriptome

Mammalian body temperature oscillates with the time of the day and is altered in diverse pathological conditions. We recently identified a body temperature-sensitive thermometer-like kinase, which alters SR protein phosphorylation and thereby globally controls alternative splicing (AS). AS can generate mRNA variants containing premature termination codons, which are degraded by nonsense-mediated decay (NMD). Here we show extensive coupling of body temperature-controlled AS to NMD, leading to global control of temperature-dependent gene expression (GE). Temperature-controlled NMD-inducing splicing events are evolutionarily conserved and pervasively found within RNA-binding proteins, including most SR proteins. NMD-inducing exons are essential for rhythmic GE of SR proteins and have a global role in establishing temperature-dependent rhythmic GE profiles, both, in mammals under circadian body temperature cycles and in plants in response to ambient temperature changes. Together, these data identify body temperature-driven AS-NMD as an evolutionary ancient, core clock-independent mechanism to generate rhythmic GE.

molecular biology↗