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At least 1,189 records · Page 66Linked to original sources
PubMed2005

Xenopus as a model organism in developmental chemical genetic screens.

Chemical genetics is a potentially powerful tool for studying developmental processes in vertebrate systems. We present data showing Xenopus laevis as a model organism in which systematic chemical genetic screens can be carried out. Previous forward chemical genetic screens, including those with developing zebrafish embryos, have demonstrated the nature and value of biological information gained with this approach. We show how amenable Xenopus is to chemical genetics by investigating a series of compounds either with known biochemical effects, or previously identified to give developmental phenotypes, on a range of biological functions, including the development of pigmentation, the heart and the central nervous system in zebrafish. We have found that the compounds give comparable phenotypes when applied to developing Xenopus embryos. We have also studied the penetrance and expressivity of these chemical genetic phenotypes in relation to genetic variation and the developmental window during which the compound is present. Finally, we assess the feasibility and the potential throughput of a screen in this vertebrate species.

Animals↗
PubMed2005

beta-Catenin: a pivot between cell adhesion and Wnt signalling.

Mutual adhesion of animal cells is intimately linked to Wnt signaling through a shared component: beta-catenin, or Armadillo in Drosophila. Recent work indicates how beta-catenin shifts from cell adhesion to Wnt signaling, a switch associated with epithelial-mesenchymal transitions and cancer.

Animals↗
PubMed2003

Galphaq and Galpha11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme.

Endothelin-A (ET(A)) is a G-protein-coupled receptor expressed in the neural crest-derived mesenchyme of the pharyngeal arches during craniofacial development. Targeted deletion of the ET(A) receptor or its ligand endothelin-1 (ET-1) causes cleft palate and hypoplasia of the mandible, otic cup, and tympanic ring. Previously we showed that Galpha(q)/Galpha(11)-null mice die around E11.0, whereas Galpha(q)((-/-))Galpha(11)((+/-)) mice survive to birth with hypomorphic phenotypes similar to, but less severe than, ET(A) or ET-1-null mice. To determine whether ET-1 signaling is transduced by Galpha(q)/Galpha(11) proteins, we examined the expression patterns of several ET-1 dependent and independent transcription factors in Galpha(q)/Galpha(11)-deficient embryos. Expression of genes encoding the ET-1-dependent transcription factors Dlx3, Dlx6, dHAND, and eHAND was specifically downregulated in the pharyngeal arches of Galpha(q)/Galpha(11)-deficient mice. In contrast, pharyngeal arch expression of the homeobox gene Msx1, which is not regulated by ET-1 signaling, was maintained in these embryos. We conclude that the Galpha(q) and Galpha(11) proteins serve as the intracellular mediators of ET-1 signaling in the pharyngeal arch mesenchyme.

Animals↗
PubMedDate not supplied

Embryonic induction: is the Nieuwkoop centre a useful concept?

Regionalisation of the amphibian embryo is classically thought to involve induction by the Spemann organiser, itself induced by the Nieuwkoop centre. This model has now been extended to teleosts, with the identification of a gene that appears to define the zebrafish equivalent of the Nieuwkoop centre.

Animals↗
PubMed2003

Chemical genetics: adding to the developmental biology toolbox.

Recent advances in cell and molecular biology have generated important tools to probe developmental questions. In addition, new genetic model systems such as Danio rerio now make large-scale vertebrate early developmental mutant screens feasible. Nonetheless, some developmental questions remain difficult to study because of the need for finer temporal, spatial, or tuneable control of gene function within a developmental system. New uses for old teratogens as well as novel chemical modulators of development have begun to fill this void.

Animals↗
PubMed2001

Molecular approaches to cerebral laterality: development and neurodegeneration.

Little is understood about the genetic or epigenetic mechanisms that underlie brain asymmetry. Because higher cognitive functions such as language, constructional and spatial abilities, and attention are organized along the left/right axis, understanding the underpinnings of this process has significant implications for both developmental biology and cognitive neuroscience. However, scientists have begun to explore, in only the most preliminary manner, the influences of subtle biologically inherited brain asymmetries on human behavior and disease. Because brain asymmetry develops prenatally, the recognition of asymmetry in neurodegeneration implies a possible relationship between the development of cerebral laterality and regional vulnerability in neurodegenerative diseases. This suggests that the study of cerebral asymmetry and laterality is likely to be relevant to a number of degenerative conditions that were previously considered to be only diseases of aging. In this article, I will outline our perspective and some of the approaches that my laboratory has begun to take to characterize the molecular basis of cerebral asymmetry. Most of these data are preliminary and the models presented are highly speculative, reflecting the primitive stage of work defining the molecular basis of cerebral asymmetry.

Brain↗
PubMed2000

Iron homeostasis: insights from genetics and animal models.

Disorders that perturb iron balance are among the most prevalent human diseases, but until recently iron transport remained poorly understood. Over the past five years, genetic studies of patients with inherited iron homeostasis disorders and the analysis of mutant mice, rats and zebrafish have helped to identify several important iron-transport proteins. With information being mined from the genomes of four species, the study of iron metabolism has benefited enormously from positional-cloning efforts. Complementing the genomic strategy, targeted mutagenesis in mice has produced new models of human iron diseases. The animal models described in this review offer valuable tools for investigating iron homeostasis in vivo.

Animals↗
PubMed2002

Role of hlx1 in zebrafish brain morphogenesis.

hlx1 is a related homeobox gene expressed in a dynamic spatiotemporal expression pattern during development of the zebrafish brain. The homologues of hlx1, mouse dbx1 and Xenopus Xdbx, are known to play a role in the specification of neurons in the spinal cord. However, the role of these molecules in the brain is less well known. We have used two different approaches to elucidate a putative function for hlx1 in the developing zebrafish brain. Blastomeres were injected with either synthetic hlx1 mRNA in gain-of-function experiments or with antisense morpholino oligonucleotides directed against hlx1 in loss-of-function experiments. Mis-expression of hlx1 produced severe defects in brain morphogenesis as a result of abnormal ventricle formation, a phenotype we referred to as "fused-brain". These animals also showed a reduction in the size of forebrain neuronal clusters as well as abnormal axon pathfinding. hlx1 antisense morpholinos specifically perturbed hindbrain morphogenesis leading to defects in the integrity of the neuroepithelium. While hindbrain patterning was in the most part unaffected there were select disruptions to the expression pattern of the neurogenic gene Zash1B in specific rhombomeres. Our results indicate multiple roles for hlx1 during zebrafish brain morphogenesis.

Animals↗
PubMed2005

The ovalbumin serpins revisited: perspective from the chicken genome of clade B serpin evolution in vertebrates.

Serpin superfamily proteins, most of which are serine protease inhibitors, share an unusual mechanism rooted in their conserved metastable tertiary structure. Although serpins have been identified in isolated members of archea, bacteria, and plants, a remarkable expansion is found in vertebrates. The chicken protein ovalbumin, a storage protein from egg white, lacking protease inhibitory activity, is an historical member of the superfamily and the founding member of the subgroup known as ov-serpins (ovalbumin-related serpins) or clade B serpins. In the human, ov-serpins include 13 proteins involved in the regulation of inflammation, apoptosis, angiogenesis, and embryogenesis. Here, a detailed analysis of the chicken (Gallus gallus) genome identified 10 clade B serpin genes that map to a single approximately 150-kb locus and contain the signature protein sequence of serpins and the gene structure of ov-serpins, with either seven or eight exons. Orthologues of PAI-2 (SERPINB2), MNEI (SERPINB1), PI-6 (SERPINB6), and maspin (SERPINB5) are highly conserved. Comparison with human ov-serpins identified avian-specific and mammal-specific genes. Importantly, a unique model of mammalian ov-serpin evolution is revealed from the comparative analysis of the chicken and human loci. The presence of a subset of ov-serpin genes in zebrafish (Danio rerio) gives insight into the ancestral locus. This comparative genomic study provides a valuable perspective on the evolutionary pathway for the clade B serpins, allowing the identification of genes with functions that may have been conserved since the origin of vertebrates. In addition, it suggests that "newer" serpins, such as ovalbumin, have contributed to vertebrate adaptation.

Amino Acid Sequence↗
PubMed2006

[Somitogenesis models and related genes in animals].

During embryonic development, many animals form a number of temporary structures along their anterior-posterior axis-somites. Cells in somites differentiate into sclerotome, which gives rise to vertebral column, dermatome, which gives rise to dermis, and myotome, which gives rise to skeletal muscle. During the past three decades, several models have been proposed to explain the formation of somites, including the clock and wavefront model, the reaction-diffusion type model, the clock and induction model, the clock and trail model, and others. These models, albeit not perfect, serve to explain different aspects of somitogenesis. Most of these models propose the concept of segmental clock. Studies on expression patterns of c-hairy 1 and c-hairy 2 in chick, l-fng in chick and mouse, and her 1 and Delta C in zebrafish have provided evidence for the existence of segmental clock.

Animals↗
PubMed2001

Green fluorescent protein (GFP) as a marker of aryl hydrocarbon receptor (AhR) function in developing zebrafish (Danio rerio).

We developed an inducible in vivo reporter system to examine expression of the aryl hydrocarbon receptor (AhR) during development in zebrafish (Danio rerio). AhR is a ligand-activated transcription factor that mediates the toxic actions of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Induction of cytochrome P4501A1 (CYP1A1) is an early biomarker of AhR activation. A 1905 base pair region of the human CYP1A1 promoter/enhancer region was regulated by AhR in zebrafish liver cells after exposure to TCDD (10 nM) in a transient transfection assay. This regulatory region was fused to the cDNA sequence encoding green fluorescent protein (GFP) of jellyfish (Aequorea victoria). Transgenic zebrafish were generated to express this AhR-regulated GFP construct. Injected fish exposed to TCDD exhibited induction of GFP in the eye, nose, and vertebrae of zebrafish embryos (48 and 72 hr after fertilization) compared to vehicle controls (DMSO), which did not express GFP. To investigate whether AhR-regulated GFP expression correlated with sites of TCDD toxicity, we exposed wild-type zebrafish to DMSO or TCDD and examined them for morphologic abnormalities. By 5 days after fertilization, TCDD-exposed fish exhibited gross dysmorphogenesis in cranio-facial and vertebral development.

Animals↗
PubMed2003

Semaphorin3a1 regulates angioblast migration and vascular development in zebrafish embryos.

Semaphorins are a large family of secreted and cell surface molecules that guide neural growth cones to their targets during development. Some semaphorins are expressed in cells and tissues beyond the nervous system suggesting the possibility that they function in the development of non-neural tissues as well. In the trunk of zebrafish embryos endothelial precursors (angioblasts) are located ventral and lateral to the somites. The angioblasts migrate medially and dorsally along the medial surface of the somites to form the dorsal aorta just ventral to the notochord. Here we show that in zebrafish Sema3a1 is involved in angioblast migration in vivo. Expression of sema3a1 in somites and neuropilin 1, which encodes for a component of the Sema3a receptor, in angioblasts suggested that Sema3a1 regulates the pathway of the dorsally migrating angioblasts. Antisense knockdown of Sema3a1 inhibited the formation of the dorsal aorta. Induced ubiquitous expression of sema3a1 in hsp70:(gfp)sema3a1(myc) transgenic embryos inhibited migration of angioblasts ventral and lateral to the somites and retarded development of the dorsal aorta, resulting in severely reduced blood circulation. Furthermore, analysis of cells that express angioblast markers following induced expression of sema3a1 or in a mutant that changes the expression of sema3a1 in the somites confirmed these results. These data implicate Sema3a1, a guidance factor for neural growth cones, in the development of the vascular system.

Animals↗
PubMed2004

Structural investigation of the ligand binding domain of the zebrafish VDR in complexes with 1alpha,25(OH)2D3 and Gemini: purification, crystallization and preliminary X-ray diffraction analysis.

The nuclear receptor of Vitamin D can be activated by a large number of agonist molecules with a wide spectrum in their stereochemical framework. Up to now most of our structural information related to the protein-ligand complex formation is based on an engineered ligand binding domain (LBD) of the human receptor. We now have extended our database, using a wild-type LBD from zebrafish that confirms the previously reported results and allows to investigate the binding of ligands that induce significant conformational changes at the protein level.

Amino Acid Sequence↗
PubMed2005

Effects of decreased muscle activity on developing axial musculature in nicb107 mutant zebrafish (Danio rerio).

The present paper discusses the effects of decreased muscle activity (DMA) on embryonic development in the zebrafish. Wild-type zebrafish embryos become mobile around 18 h post-fertilisation, long before the axial musculature is fully differentiated. As a model for DMA, the nic(b107) mutant was used. In nic(b107) mutant embryos, muscle fibres are mechanically intact and able to contract, but neuronal signalling is defective and the fibres are not activated, rendering the embryos immobile. Despite the immobility, distinguished slow and fast muscle fibres developed at the correct location in the axial muscles, helical muscle fibre arrangements were detected and sarcomere architecture was generated. However, in nic(b107) mutant embryos the notochord is flatter and the cross-sectional body shape more rounded, also affecting muscle fibre orientation. The stacking of sarcomeres and myofibril arrangement show a less regular pattern. Finally, expression levels of several genes were changed. Together, these changes in expression indicate that muscle growth is not impeded and energy metabolism is not changed by the decrease in muscle activity but that the composition of muscle is altered. In addition, skin stiffness is affected. In conclusion, the lack of muscle fibre activity did not prevent the basal muscle components developing but influenced further organisation and differentiation of these components.

Animals↗
PubMed2002

Animal models for the genetic study of human alcohol phenotypes.

Researchers are increasingly using animal models to study the genetic basis of complex human behaviors, such as alcoholism. The most commonly used animal species are rodents, but other species, such as nonhuman primates, fruit flies, and zebrafish, can also provide important information. A variety of approaches are employed in these studies, particularly knockout and transgenic mice as well as specially bred animal lines that can be used for various genetic analyses, including quantitative trait locus mapping. Other strategies applied in genetic studies in animal models include random mutagenesis, virus-mediated gene transfer, and gene expression profiling.

Alcoholism↗