Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.01.23.576882

Underlying molecular effects to behavioral consequences present line of evidence for zebrafish eye development and function alteration by crude oil exposure.

Abstract

Crude oil can affect the normal eye development and swimming behavior of fish embryos. In this study 0-4 hours post fertilization (hpf) zebrafish (Danio rerio) embryos were exposed to low, sublethal concentrations of water-accommodated fractions (WAF) of a naphthenic North Sea crude oil alone and in combination with a third-generation chemical dispersant. Effects on eye development and function at the transcript, histological, morphological, and behavioral level were assessed relative to untreated control specimen at 119 hpf. Exposed embryos swam significantly less during the dark phases of the light/dark transition test. Eye size of zebrafish embryos was significantly smaller in groups exposed to crude oil WAFs. Zebrafish retina histology revealed that, among other structural alterations, the outer nuclear layer, containing photoreceptor cells relevant for normal visual functioning, was significantly thinner in exposed embryos. Transcriptome analysis revealed that several genes involved in eye development and function (opsins and crystallins) were dysregulated upon oil exposure. The molecular effects on gene expression and eye histology results form a novel line of evidence that explains the observed effects of crude oil on the swimming activity of exposed fish embryos. The present study is in line with recent findings highlighting the importance of ocular toxicity in developing embryos exposed to petroleum samples at environmentally relevant and non-lethal concentrations without visible malformations. The study suggests that oculotoxicity should be considered as a major toxicity pathway alongside to the well-established cardiotoxicity.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mueller, L. K., Johann, S., Denecke, B., Abdallah, A. T., Hecker, M., Hollert, H., Seiler, T.-B.. 2024-01-24. Underlying molecular effects to behavioral consequences present line of evidence for zebrafish eye development and function alteration by crude oil exposure.. https://doi.org/10.1101/2024.01.23.576882

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A bicistronic Aldh1a3-P2A-TagBFP knock-in reporter mouse line for studying genitourinary tract development

Aldehyde dehydrogenase 1a3 (Aldh1a3) is an enzyme involved in retinoic acid synthesis with dynamic expression patterns during development, including in the urogenital system. Here, we generated a bicistronic Aldh1a3-P2A-TagBFP knock-in mouse using CRISPR/Cas9 genome editing, inserting TagBFP immediately upstream of the endogenous Aldh1a3 stop codon. Correct targeting was confirmed by Oxford Nanopore long-read sequencing, and heterozygous and homozygous mice were viable and fertile without overt morphological abnormalities. TagBFP fluorescence faithfully overlapped with endogenous Aldh1a3 immunoreactivity and reproduced established expression domains in the developing craniofacial region, intestine, kidney, and broader urogenital system. Extensive characterization of the urogenital system revealed dynamic, spatially restricted BFP reporter activity in Aldh1a3-expressing domains across several key structures, including the ureteric bud and collecting duct lineage, seminal vesicles, caput epididymis, and developing uterine horns. The Aldh1a3-P2A-TagBFP mouse provides a fluorescent resource for visualizing Aldh1a3 expression across development and in adult tissues, including for the characterization of Aldh1a3-expressing domains in the urogenital system. The relatively low fluorescence intensity of TagBFP should be considered when assessing low-level reporter expression.

developmental biology↗

Translation of a small upstream open reading frame functions as a rheostat for the regulation of lin-41 by the Let-7 microRNA in Caenorhabditis elegans

MicroRNAs have been likened to the "dark matter" of eukaryotic genomes, reflecting their pervasive regulatory influence. MicroRNAs were first identified through genetic studies of developmental timing in the nematode Caenorhabditis elegans. Let-7 was the first microRNA recognized to be broadly conserved. The principal target of Let-7 in the developmental timing pathway is the TRIM-NHL RNA-binding protein LIN-41. During the L4 larval stage, Let-7 represses lin-41 translation by binding to two Let-7 complementary sites in the lin-41 3'UTR. Despite the importance of microRNA-based translational regulation, the underlying molecular mechanisms are incompletely understood. Through genetic analysis, we discovered an unrecognized feature of the mechanism by which Let-7 controls lin-41 translation. This mechanism requires a 5'-regulatory exon containing a seven-amino acid upstream open reading frame (uORF) and conserved sequence elements. Genome editing indicates that the specific uORF amino acid sequence itself is not important. Our data suggest that uORF translation and 5'UTR structure limit initiation at the downstream lin-41 start codon, enabling tight control by Let-7. Without this mechanism, the Let-7 microRNA is unable to properly regulate lin-41 to enable proper development.

developmental biology↗

Ductal myofibroblasts reactivate contractile program to stabilize alveolar architecture during lung regeneration

The alveolar sac architecture is essential for efficient gas exchange and must be precisely maintained throughout life; however, how this delicate structure is preserved during adult regeneration remains poorly understood. Using a mouse pneumonectomy model, we found that Lgr6+ Hhip+ ductal myofibroblasts, a poorly characterized mesenchymal population, are indispensable for maintaining alveolar integrity during lung regrowth. Comprehensive characterization using single-cell transcriptomics, mouse genetics, and pharmacological assays demonstrated that these ductal myofibroblasts secrete myogenic factors, most notably CCN4, to reactivate a myogenic program that converts them into contractile PA-DMFs, thereby preserving alveolar architecture. Lineage-tracing further revealed that these ductal myofibroblasts originate from embryonic MCAM- SMA+ distal progenitors via subepithelial TGF-{beta} signaling, serving as a lifelong guardian of alveolar structural integrity. Notably, cross-species analysis identified an analogous population of LGR6+ fibromyocytes in human respiratory bronchioles. Together, these findings indicate ductal myofibroblasts as a developmentally programmed cell population that reactivate a contractile program to structurally support the regeneration of adult lungs.

developmental biology↗