Effects of lithium on pigmentation in the embryonic zebrafish (Brachydanio rerio). (1/1835)

Pigment cell precursors of the embryonic zebrafish give rise to melanophores, xanthophores and/or iridophores. Cell signaling mechanisms related to the development of pigmentation remain obscure. In order to examine the mechanisms involved in pigment cell signaling, we treated zebrafish embryos with various activators and inhibitors of signaling pathways. Among those chemicals tested, LiCl and LiCl/forskolin had a stimulatory effect on pigmentation, most notable in the melanophore population. We propose that the inositol phosphate (IP) pathway, is involved in pigment pattern formation in zebrafish through its involvement in the: (1) differentiation/proliferation of melanophores; (2) dispersion of melanosomes; and/or (3) synthesis/deposition of melanin. To discern at what level pigmentation was being effected we: (1) counted the number of melanophores in control and experimental animals 5 days after treatment; (2) measured tyrosinase activity and melanin content; and (3) employed immunoblotting techniques with anti-tyrosine-related protein-2 and anti-melanocyte-specific gene-1 as melanophore-specific markers. Although gross pigmentation increased dramatically in LiCl- and LiCl/forskolin treated embryos, the effect on pigmentation was not due to an increase in the proliferation of melanophores, but was possibly through an increase in melanin synthesis and/or deposition. Collectively, results from these studies suggest the involvement of an IP-signaling pathway in the stimulation of pigmentation in embryonic zebrafish through the synthesis/deposition of melanin within the neural crest-derived melanophores.  (+info)

Flavin nucleotides in human lens: regional distribution in brunescent cataracts. (2/1835)

The biochemical mechanism(s) underlying brunescent cataracts remain unclear. Oxidative stress due to reactive oxygen species may have a role in the pigmentation process in eye lens. We have analysed human cataractous lenses for flavins by high-performance liquid chromatography (HPLC), since flavins are light sensitive and act as endogenous sensitizers generating reactive oxygen species in the eye. The most significant observation in this study is that higher levels of flavin nucleotides occur in brown lens compared to yellow lens. The concentration of flavin nucleotides (flavin monouncleotide, FMN + flavin adenine dinucleotide, FAD) was highest in the nuclear region of the lens followed by the cortical and capsule-epithelial regions. However, the ratio of FAD/FMN was lowest in the nuclear region of the lens followed by other regions. On the other hand, riboflavin was not detected in any of the lens (cataractous) regions. These results suggest that the observed increase in flavin nucleotides in the ocular tissue could contribute towards deepening of lens pigmentation.  (+info)

Stripe formation in juvenile Pomacanthus explained by a generalized turing mechanism with chemotaxis. (3/1835)

Current interest in pattern formation can be traced to a seminal paper by Turing, who demonstrated that a system of reacting and diffusing chemicals, called morphogens, can interact so as to produce stable nonuniform concentration patterns in space. Recently, a Turing model has been suggested to explain the development of pigmentation patterns on species of growing angelfish such as Pomacanthus semicirculatus, which exhibit readily observed changes in the number, size, and orientation of colored stripes during development of juvenile and adult stages, but the model fails to predict key features of the observations on stripe formation. Here we develop a generalized Turing model incorporating cell growth and movement, we analyze the effects of these processes on patterning, and we demonstrate that the model can explain important features of pattern formation in a growing system such as Pomacanthus. The applicability of classical Turing models to biological pattern formation is limited by virtue of the sensitivity of patterns to model parameters, but here we show that the incorporation of growth results in robustly generated patterns without strict parameter control. In the model, chemotaxis in response to gradients in a morphogen distribution leads to aggregation of one type of pigment cell into a striped spatial pattern.  (+info)

Down-regulation of melanocortin receptor signaling mediated by the amino terminus of Agouti protein in Xenopus melanophores. (4/1835)

Agouti protein and Agouti-related protein (Agrp) regulate pigmentation and body weight, respectively, by antagonizing melanocortin receptor signaling. A carboxyl-terminal fragment of Agouti protein, Ser73-Cys131, is sufficient for melanocortin receptor antagonism, but Western blot analysis of skin extracts reveals that the electrophoretic mobility of native Agouti protein corresponds to the mature full-length form, His23-Cys131. To investigate the potential role of the amino-terminal residues, we compared the function of full-length and carboxyl-terminal fragments of Agrp and Agouti protein in a sensitive bioassay based on pigment dispersion in Xenopus melanophores. We find that carboxyl-terminal Agouti protein, and all forms of Agrp tested, act solely by competitive antagonism of melanocortin action. However, full-length Agouti protein acts by an additional mechanism that is time- and temperature-dependent, depresses maximal levels of pigment dispersion, and is therefore likely to be mediated by receptor down-regulation. Apparent down-regulation is not observed for a mixture of amino-terminal and carboxyl-terminal fragments. We propose that the phenotypic effects of Agouti in vivo represent a bipartite mechanism: competitive antagonism of agonist binding by the carboxyl-terminal portion of Agouti protein and down-regulation of melanocortin receptor signaling by an unknown mechanism that requires residues in the amino terminus of the Agouti protein.  (+info)

The permeability to cytochalasin B of the new unpigmented surface in the first cleavage furrow of the newt's egg. (5/1835)

Two of 10 mug/ml cytochalasin B (CB) caused retraction of the first cleavage furrow in Triturus eggs, a spreading of the unpigmented surface from the furrow region and a flattening of the whole egg. CB appears to act against the contractility of the microfilamentous band at mid-cleavage so as to relax the furrow and also to weaken unpigmented surface to allow the egg to flatten. Uncleaved eggs and the initial formation of the cleavage groove were unaffected by CB. A fully-retracted first cleavage furrow reformed itself on transfer of the egg to normal medium but only at the time of second cleavage. Initiation of second cleavage depended upon there being sufficient of the original pigmented surface on the animal hemisphere. Tritium-labelled CB of high specific activty was prepared and used to study its ability to penetrate the surface of newt eggs during cleavage. Scintillation couting of whole eggs showed that CB was not taken into the newt egg until mid-cleavage (about 17 min after the double stripe stage) when new surface began to spread in the cleavage furrow. Fixation in glutaraldehyde and osmium tetroxide retained radioactivity in the egg, but more CB was retained after fixation in osmium tetroxide alone than after double fixation. Most of the retained radioactivity was in yolk platelets. Autoradiographs were prepared to sectioned eggs which had been fixed at late cleavage after [3H]CB had flattend the furrow. These showed that CB entered the egg through the unpigmented surface which formed in the furrow but it could not enter through the pigmented surface. The impermeability of the pigmented surface explains the observations that CB does not prevent initial furrowing at cleavage. Once inside the egg CB is transported slowly. CB penetrates to a limited extent beneath the pigmented surface from its border with the unpigmented surface in the first cleavage furrow and this seems insufficient in some circumstances to suppress the contractile phase of second cleavage.  (+info)

Deposition of [3H]cocaine, [3H]nicotine, and [3H]flunitrazepam in mouse hair melanosomes after systemic administration. (6/1835)

Microautoradiography was employed to show that association of drugs from the serum directly with forming hair pigment is a primary pathway of deposition into the hair. After systemic administration of [3H]flunitrazepam, [3H]nicotine, and [3H]cocaine, association of all three drugs with melanin in the forming hair was observed within minutes of dosage. Sebum was determined to be an insignificant deposition route for all three drugs. Pigmented mice had significantly higher concentrations of all three drugs than did nonpigmented mice. The results provide a better basis for ultimately using hair for reliable analysis of drug and environmental toxin exposure.  (+info)

Natural copepods are superior to enriched artemia nauplii as feed for halibut larvae (Hippoglossus hippoglossus) in terms of survival, pigmentation and retinal morphology: relation to dietary essential fatty acids. (7/1835)

Replicate groups of halibut larvae were fed to d 71 post-first feeding (PFF) either the marine copepod, Eurytemora velox, or Artemia nauplii doubly enriched with the marine chromist or golden algae, Schizochytrium sp., (Algamac 2000) and a commercial oil emulsion (SuperSelco). The fatty acid compositions of eyes, brains and livers from larvae fed the two diets were measured, and indices of growth, eye migration and skin pigmentation were recorded along with histological examinations of eye and liver. The docosahexaenoic acid [22:6(n-3); DHA]/eicosapentaenoic acid [20:5(n-3); EPA] ratios in Artemia nauplii enriched with the SuperSelco and Algamac 2000 were 0.4 and 1.0, respectively. The E. velox copepods were divided into two size ranges (125-250 and 250-400 microm) with the smaller size range containing the highest level of (n-3) highly unsaturated fatty acids (HUFA). The DHA/EPA ratios for the two size ranges of copepods were 2.0 and 0.9, respectively. The total lipids of eyes, brains and livers of larvae fed copepods had higher levels of DHA and lower levels of EPA than those of larvae fed enriched Artemia. The percentage of survival of the halibut larvae was significantly higher when copepods rather than enriched Artemia nauplii were fed, but larval specific growth rates did not differ. The indices of eye migration were high and not significantly different in larvae fed the two diets, but the percentage of larvae undergoing successful metamorphosis (complete eye migration and dorsal pigmentation) was higher in larvae fed copepods (40%) than in larvae fed enriched Artemia (4%). The rod/cone ratios in histological sections of the retina were 2.5 +/- 0.7 in larvae fed copepods and 1.3 +/- 0.6 in larvae fed enriched Artemia (P < 0.01). Histological examination of the livers and intestines of the larvae were consistent with better assimilation of lipid from copepods than lipid from Artemia nauplii up to 46 d post-first feeding. Thus, marine copepods are superior to enriched Artemia as food for halibut larvae in terms of survival, eye development and pigmentation, and this superiority can be related to the level of DHA in the feed.  (+info)

Notch-mediated segmentation and growth control of the Drosophila leg. (8/1835)

The possession of segmented appendages is a defining characteristic of the arthropods. By analyzing both loss-of-function and ectopic expression experiments, we show that the Notch signaling pathway plays a fundamental role in the segmentation and growth of the Drosophila leg. Local activation of Notch is necessary and sufficient to promote the formation of joints between segments. This segmentation process requires the participation of the Notch ligands, Serrate and Delta, as well as Fringe. These three proteins are each expressed in the developing leg and antennal imaginal discs in a segmentally repeated pattern that is regulated downstream of the action of Wingless and Decapentaplegic. Our studies further show that Notch activation is both necessary and sufficient to promote leg growth. We also identify target genes regulated both positively and negatively downstream of Notch signaling that are required for normal leg development. Together, these observations outline a regulatory hierarchy for the segmentation and growth of the leg. The Notch pathway is also deployed for segmentation during vertebrate somitogenesis, which raises the possibility of a common origin for the segmentation of these distinct tissues.  (+info)