Mammalian liver-X-receptors (LXRs) are transcription factors activated by oxysterols. They play an essential role in lipid and glucose metabolism. We have cloned the open reading frame of zebrafish lxr and describe its genomic organization. Zebrafish lxr encodes a 50-kDa protein with high sequence similarity to mammalian LXR alpha. In transfection assays, the encoded protein showed transcriptional activity in response to LXR-ligands. Treatment of adult zebrafish with the synthetic LXR ligand, GW3965, induced expression of genes involved in hepatic cholesterol and lipid pathways. Using qPCR and in situ hybridization, we found ubiquitous expression of lxr mRNA during the first 24 hr of development, followed by more restricted expression, particularly to the liver at 3dpf and the liver and intestine at 4dpf. In adult fish, all examined organs expressed lxr. In addition to a metabolic role of lxr, the temporal expression pattern suggests a developmental role in, e.g., the liver and CNS.

The Caenorhabditis elegans genome encodes ten proteins that share similarity with Hedgehog through the C-terminal Hint/Hog domain. While most genes are members of larger gene families, qua-1 is a single copy gene. Here we show that orthologs of qua-1 exist in many nematodes, including Brugia malayi, which shared a common ancestor with C. elegans about 300 million years ago. The QUA-1 proteins contain an N-terminal domain, the Qua domain, that is highly conserved, but whose molecular function is not known. We have studied the expression pattern of qua-1 in C. elegans using a qua-1::GFP transcriptional fusion. qua-1 is mainly expressed in hyp1 to hyp11 hypodermal cells, but not in seam cells. It is also expressed in intestinal and rectal cells, sensilla support cells, and the P cell lineage in L1. The expression of qua-1::GFP undergoes cyclical changes during development in phase with the molting cycle. It accumulates prior to molting and disappears between molts. Disruption of the qua-1 gene function through an internal deletion that causes a frame shift with premature stop in the middle of the gene results in strong lethality. The animals arrest in the early larval stages due to defects in molting. Electron microscopy reveals double cuticles due to defective ecdysis, but no obvious defects are seen in the hypodermis. Qua domain-only::GFP and full-length QUA-1::GFP fusion constructs are secreted and associated with the overlying cuticle, but only QUA-1::GFP rescues the mutant phenotype. Our results suggest that both the Hint/Hog domain and Qua domain are critically required for the function of QUA-1.

The vertebrate retina is very well conserved in evolution. Its structure and functional features are very similar in phyla as different as primates and teleost fish. Here, we describe the spatiotemporal characteristics of neurogenesis in the retina of a teleost, medaka, and compare them with other species, primarily the zebrafish. Several intriguing differences are observed between medaka and zebrafish. For example, photoreceptor differentiation in the medaka retina starts independently in two different areas, and at more advanced stages of differentiation, medaka and zebrafish retinae display obviously different patterns of the photoreceptor cell mosaic. Medaka and zebrafish evolutionary lineages are thought to have separated from each other 110 million years ago, and so the differences between these species are not unexpected, and may be exploited to gain insight into the architecture of developmental pathways. Importantly, this work highlights the benefits of using multiple teleost models in parallel to understand a developmental process.

Drosophila Dappled (DPLD) is a member of the RBCC/TRIM superfamily, a protein family involved in numerous diverse processes such as developmental timing and asymmetric cell divisions. DPLD belongs to the LIN-41 subclade, several members of which are micro RNA (miRNA) regulated. We re-examined the LIN-41 subclade members and their relation to other RBCC/TRIMs and dpld paralogs, and identified a new Drosophila muscle specific RBCC/TRIM: Another B-Box Affiliate, ABBA. In silico predictions of candidate miRNA regulators of dpld identified let-7 as the strongest candidate. Overexpression of dpld led to abnormal eye development, indicating that strict regulation of dpld mRNA levels is crucial for normal eye development. This phenotype was sensitive to let-7 dosage, suggesting let-7 regulation of dpld in the eye disc. A cell-based assay verified let-7 miRNA down-regulation of dpld expression by means of its 3'-untranslated region. Thus, dpld seems also to be miRNA regulated, suggesting that miRNAs represent an ancient mechanism of LIN-41 regulation.