Effect of juvenoids and retinoic acid on the development or larva and nymphs of the tick Ixodes ricinus L. (Acari: Ixodidae) and regeneration of Haller's organ during metamorphosis

Larvae and nymphae of the tick Ixodes ricinus L. display similar reactions to analogs of the insect juvenile hormones (methopren and pyriproxyfen), which induce at both stages juvenalization of the Haller's sense organ regenerates. Similar effects were also described for retinoic acid. Unlike juvenoids, retinoic acid can affect not only regeneration, but also normal development of the Haller's organ and cause changes corresponding to so-called regenerative induction. Amputation of the leg and treatment with retinoic acid do not affect the duration of larval or nymphal development, while juvenoids somewhat accelerate their development.     

Specific Features of Haller's Organ Regeneration in the Tick Haemaphysalis longicornis (Acari,Ixodidae) in the Presence of Methoprene and Retinoic Acid

The results of experiments on regeneration of the Haller's sensory organ in the metastriate ixodid tick Haemaphysalis longicornisNeumann in the presence of the juvenoid methoprene and retinoic acid and of studies of its structural changes by SEM confirmed the similarity of prostriate and metastriate ixodids as concerns the juvenalizing effect of the above morphogens on regenerative processes during nymphal-imaginal metamorphosis. However, the metastriate ticks (Haemaphysalis and earlier studied Hyalomma) are well behind the prostriate ticks (Ixodes) as concerns the extent of changes induced by juvenoids and retinoids in the sensillar sets of Haller's organ regenerates.     

Effect of of methoprene and retinoic acid on characteristics of Haller's organ regeneration in the tick Haemaphysalis longicornis (Acari, Ixodidae)

The results of experiments on regeneration of the Haller's sensory organ in the metastriate ixodid tick Haemaphysalis longicornis Neumann in the presence of the juvenoid methoprene and retinoic acid and of studies of its structural changes by SEM confirmed the similarity of prostriate and metastriate ixodids as concerns the juvenalizing effect of the above morphogens on regenerative processes during nymphal-imaginal metamorphosis. However, the metastriate ticks (Haemaphysalis and earlier studied Hyalomma) are well behind the prostriate ticks (Ixodes) as concerns the extent of changes induced by juvenoids and retinoids in the sensillar sets of Haller's organ regenerates.     

Retinoic acid modulates the pattern of cell division in embryos ofLymnaea stagnalis (Mollusca)

All-trans retinoic acid is well known as a modulator of positional specification in vertebrate development. A similar mechanism may operate in molluscan development. Molluscan development is characterized by an invariant pattern of cell divisions, which allows the study of individual cells in the developing organism. Low concentrations of exogenous retinoic acid applied during gastrulation affect the cell division pattern in the early larval stage of the molluscLymnaea stagnalis. A few cells from the apical plate, a larval organ consisting of seven large cleavage-arrested cells, were induced by retinoic acid to resume cell division. They typically formed an area of proliferating small cells that resembles the adjacent areas of precursor cells of adult ectoderm. The identification of individual cells that are transformed by retinoic acid may provide new insights into the mechanisms underlying positional specification within the embryo.     

All-trans-retinoic acid-mediated modulation of p53 during neural differentiation in murine embryonic stem cells

All-trans-retinoic acid (RA) plays an important physiological role in embryonic development and is teratogenic in large doses in almost all species. p53, a tumor suppressor gene encodes phosphoproteins, which regulate cellular proliferation, differentiation, and apoptosis. Temporal modulation of p53 by retinoic acid was investigated in murine embryonic stem cells during differentiation and apoptosis. Undifferentiated embryonic stem cells express a high level of p53 mRNA and protein followed by a decrease in p53 levels as differentiation proceeds. The addition of retinoic acid during 8–10 days of differentiation increased the levels of p53 mRNA and protein, accompanied by accelerated neural differentiation and apoptosis. Marked increase in apoptosis was observed at 10–20 h after retinoic acid treatment when compared with untreated controls. Retinoic acid-induced morphological differentiation resulted in predominantly neural-type cells. Maximum increase in p53 mRNA in retinoic acid-treated cells occurred on day 17, whereas maximum protein synthesis occurred on days 14–17, which coincided with increased neural differentiation and proliferation. Increased p53 levels did not induce p21 transactivation, interestingly a decrease in p21 was observed on day 17 on exposure to retinoic acid. The level of p53 declined by day 21 of differentiation. The results demonstrated that retinoic acid-mediated apoptosis preceded the changes in p53 expression, suggesting that p53 induction does not initiate retinoic acid-induced apoptosis during development. However, retinoic acid accelerated neural differentiation and increased the expression of p53 in proliferating neural cells, corroborated by decreased p21 levels, indicating the importance of cell type and stage specificity of p53 function. This revised version was published online in July 2006 with corrections to the Cover Date.     

miR-196 regulates axial patterning and pectoral appendage initiation

Vertebrate Hox clusters contain protein-coding genes that regulate body axis development and microRNA (miRNA) genes whose functions are not yet well understood. We overexpressed the Hox cluster microRNA miR-196 in zebrafish embryos and found four specific, viable phenotypes: failure of pectoral fin bud initiation, deletion of the 6th pharyngeal arch, homeotic aberration and loss of rostral vertebrae, and reduced number of ribs and somites. Reciprocally, miR-196 knockdown evoked an extra pharyngeal arch, extra ribs, and extra somites, confirming endogenous roles of miR-196. miR-196 injection altered expression of hox genes and the signaling of retinoic acid through the retinoic acid receptor gene rarab. Knocking down rarab mimicked the pectoral fin phenotype of miR-196 overexpression, and reporter constructs tested in tissue culture and in embryos showed that the rarab 3′UTR is a miR-196 target for pectoral fin bud initiation. These results show that a Hox cluster microRNA modulates development of axial patterning similar to nearby protein-coding Hox genes, and acts on appendicular patterning at least in part by modulating retinoic acid signaling.     

Sense organs in post-embryonic stages of Hyalomma marginatum marginatum Koch, 1844 (Acari: Ixodida: Ixodidae). I. Tarsal sensory system.

Light and scanning electron microscopic studies showed the differences in morphology and in size of Haller's organ in larvae, nymphs and adults (females and males) of Hyalomma marginatum marginatum Koch, 1844. The length of the anterior pit setae increases during post-embryonic development. The localization of these setae is the same in all stages. Six setae (one porose seta, two grooved setae, two fine setae, one conical seta) contain anterior pit of various developmental stages. In nymphs and adults more numerous pores appear on the wall surface of porose seta than in the larval stage. The structure of the capsule roof also differs in various developmental stages. Haller's organ of Hyalomma m. marginatum shows great degree of morphological development which is connected with the complicated life cycle and feeding behaviour of this tick species.     

Retinoic Acid-Induced blr1 Expression Promotes ERK2 Activation and Cell Differentiation in HL-60 Cells

Retinoids are known to induce the differentiation and cell cycle arrest of human myeloid leukemia cells in vitro. Differential display was used to identify putative early regulatory genes that are differentially expressed in HL-60 human promyelocytic leukemia cells treated with retinoic acid. One of the cDNAs cloned encodes sequences identifying Burkitt's lymphoma receptor 1 (BLR1), a recently described chemokine receptor. Northern blot analysis demonstrates that blr1 mRNA expression increases within 9 h of retinoic acid treatment, well before functional differentiation or G₁/G₀ growth arrest at 48 h or onset of morphological changes, suggesting a possible regulatory function. The expression of blr1 mRNA is transient, peaking at 72 h when cells are differentiated. blr1 mRNA also is induced by other differentiation-inducing agents, 1α,25-dihydroxyvitamin D₃ and DMSO. Induction of blr1 mRNA by retinoic acid is not blocked by the protein synthesis inhibitor cycloheximide. In HL-60 cells stably transfected with blr1 cDNA, ectopic expression of blr1 causes an increase in ERK2 MAPK activation and promotes retinoic acid-induced G₁/G₀ growth arrest and cell differentiation. The early expression of blr1 mRNA during differentiation, its ability to increase ERK2 activation, and its enhancement of retinoic acid-induced differentiation suggest that blr1 expression may be involved in retinoic acid-induced HL-60 differentiation.     

Retinoic acid signaling is necessary for the development of the organ of Corti.

The cellular mosaic of the mammalian organ of Corti represents one of the most highly ordered structures in any vertebrate system. A single row of inner hair cells and three or four rows of outer hair cells extend along the basal-to-apical axis of the cochlea. The factors that play a role in the development of specific cell types within the cochlea are largely unknown; however, the results of previous studies have strongly suggested that retinoic acid plays a role in the development of cells as hair cells. To determine whether cochlear progenitor cells can respond directly to retinoic acid, the expression patterns for each of the RAR and RXR receptors within the embryonic cochlear duct were determined by in situ hybridization. Results indicate that RARalpha, RXRalpha, and RXRgamma are initially expressed throughout the cochlear duct. As development continues, the expression of each receptor becomes more intense in cells that will develop as hair cells. At the same time, receptor expression is down-regulated in cells that will develop as nonsensory cell types. To determine the effects of retinoic acid signaling during the development of the organ of Corti, activation of retinoid receptors was blocked in cultures of the embryonic cochlea through receptor-specific antagonism or inhibition of retinoic acid synthesis. Results indicate that inhibition of retinoic acid signaling induces a significant decrease in the number of cells that develop as hair cells and a disruption in the development of the organ of Corti. These results demonstrate that cells within the developing cochlea can respond to retinoic acid and that signaling by retinoic acid is necessary for the normal development of the organ of Corti.     

The Haller's organ roof and anterior pit setae of Argas ticks (Ixodoidea: Argasidae). Subgenera Secretargas and Ogadenus

Adults of the Argas subgenera Secretargas (3 species) and Ogadenus (1 species) were studied by scanning electron microscopy. In each species, the anterior pit and Haller's organ are situated in a large dorsal hump of Tarsus I and the 9 setae of the anterior pit are characteristic of the genus Argas in structure and numbers. In A. (S.) transgariepinus, an Ethiopian-Palearctic crevice-dwelling parasite of bats, the Haller's organ capsule roof is solid with a slitlike transverse aperture. In A. (S.) hoogstraali and A. (S.) echinops, Malagasy soil-dwelling parasites of Oplurus (Varanidae) lizards and the hedgehog-tenrec (Insectivora: Tenrecidae), respectively, the Haller's organ is virtually unroofed but partially screened by arborescent dorsal projections from the posterior wall of the capsule, and the open capsule contains numerous fine pleomorphs. In A. (O.) brumpti, a soil-dwelling parasite of the hyrax (Procavia), other terrestrial mammals, and lizards in the Ethiopian Region, the capsule is also virtually unroofed and contains numerous fine pleomorphs. The unroofed capsule is probably phylogenetically primitive and occurs only in these 3 and 2 other Argas species. The soil microhabitat (in Argas confined to 3 of the 4 species recorded here), and the reptile or ancient mammal hosts of these 3 species, as well as the zoogeographical isolation of 2 of the species in the Malagasy Region, are distinctive in this genus of 56 species. The interrelationships between an unroofed Haller's organ capsule and unusual biological properties remain to be determined.     

Regeneration of Haller's sensory organ in the tick, Ixodes rubicundus (Acari: Ixodidae)

A study of regeneration in nymphs and adults of the South African tick Ixodes (Afrixodes) rubicundus, from which the forelegs had been amputated during the previous instar, revealed that the structural changes in regenerated Haller's sensory organs resemble those observed in other ixodid ticks, in particular in another prostriate tick, Ixodes (Ixodes) ricinus. The adult regenerates re-establish their atavistic features in terms of the increased number of different sensilla on the distal knoll, in the anterior pit and the capsule. The nymphal regenerates, in contrast, re-establish the features of the previous instar through a reduction in the number of some sensilla on the distal knoll and in the post-capsular area. The structural changes in different compartments of the organ appear independent. The phenomenon of regenerative induction through the appearance of specific changes in Haller's organ of the contralateral non-treated foreleg is probably characteristic only of prostriate ticks. A unique modification in the regenerated Haller's organ as revealed by duplication of the Haller's organ capsule was discovered in both I. rubicundus nymphs and adult ticks.     

Developmental analyses reveal early arrests of the spore-bearing parts of reproductive organs in unisexual flowers of cucumber (<Emphasis Type="Italic">Cucumis sativus</Emphasis> L.)

To understand the regulatory mechanisms governing unisexual flower development in cucumber, we conducted a systematic morphogenetic analysis of male and female flower development, examined the dynamic changes in expression of the C-class floral organ identity gene CUM1, and assessed the extent of DNA damage in inappropriate carpels of male flowers. Accordingly, based on the occurrence of distinct morphological events, we divided the floral development into 12 stages ranging from floral meristem initiation to anthesis. As a result of our investigation we found that the arrest of stamen development in female flowers, which occurs just after the differentiation between the anther and filament, is mainly restricted to the primordial anther, and that it is coincident with down-regulation of CUM1 gene expression. In contrast, the arrest of carpel development in the male flowers occurs prior to the differentiation between the stigma and ovary, given that no indication of ovary differentiation was observed even though CUM1 gene expression remained detectable throughout the development of the stigma-like structures. Although the male and female reproductive organs have distinctive characteristics in terms of organ differentiation, there are two common features regarding organ arrest. The first is that the arrest of the inappropriate organ does not affect the entirety of the organ uniformly but occurs only in portions of the organs. The second feature is that all the arrested portions in both reproductive organs are spore-bearing parts.Abbreviations SEM Scanning electron microscopy - TEM Transmission electron microscopy - TUNEL TdT-mediated dUTP nick-end labeling     

视黄类受体与视黄酸致畸作用关系

视黄酸（维甲酸）可引起包括人在内的多种动物胚胎畸形,其生物活性是由一系列视黄酸受体及其配体介导的。其中视黄类受体RAR起主要作用,RAR的配体为强致畸物,相对致畸活性由强至弱依次为配体α、配体β和配体γ。视黄酸受体RXR的配体无致畸活性,但是可加强RAR激动剂的某些致畸郊应。视黄酸受体还可通过其它基因的表达而影响胚胎发育。对视黄类受体基因突变和不同视黄类受体及其配体与致畸作用的关系,以及此类受体对其它基因表达的调节作简要综述。 Abstract: Retinoic acid can induce teratogenesis of the fetus of many animals including human, and its biological activities are induced by a serious of different retinoic acid accepters and their ligands. The retinoic acid acceptor RAR plays key roles in the teratogenesis, and the legands of RAR are strong teratogens. The intensity sequence of the relative teratogenesis is ligandα、ligandβ and ligandγ. The ligands of the retinoic acid acceptor RXR cannot induce teratogenesis, but they can enhance the teratogenesis of the RAR stimulus. The retinoic acid acceptors can also affect the development of the fetus by adjusting the expression of the other genes. The relations between the gene mutation of the retinoic acid acceptor, various retinoic acid acceptors and their ligands and teratogenesis of retinoic acid are summarized in this article. In addition, the regulations of the retinoic acid acceptors to the other genes are also discussed.     

Unravelling of physiological functions of retinoids using a dominant-negative retinoic acid receptor

We have constructed dominant-negative retinoic acid receptors by substituting a single amino acid which has been found in a dominant-negative thyroid hormone receptor, and have expressed the dominant-negative retinoic acid receptors in the epidermis, a potential target organ of retinoic acid. The resultant transgenic mice exhibited dramatic suppression of epidermal development, demonstrating the absolute requirement of retionic acid in normal skin development. This novel method, targeted expression of the dominant-negative receptor, is theoretically applicable to any organ, thus opening the way to defining the physiological roles of retionic acid as well as other lipophilic hormones during embryogenesis as well as in adults     

Pharmacological evidence for the role of RAR in axon guidance and embryonic development of a protostome species

Retinoic acid (RA), the active metabolite of vitamin A, functions through nuclear receptors, one of which is the retinoic acid receptor (RAR). Though the RAR is essential for various aspects of vertebrate development, little is known about the role of RAR in nonchordate invertebrates. Here, we examined the potential role of an invertebrate RAR in mediating chemotropic effects of retinoic acid. The RAR of the protostome Lymnaea stagnalis is present in the growth cones of regenerating cultured motorneurons, and a synthetic RAR agonist (EC23), was able to mimic the effects of retinoic acid in inducing growth cone turning. We also examined the ability of the natural retinoids, all‐trans RA and 9‐cis RA, as well as the synthetic RAR agonists, to disrupt embryonic development in Lymnaea. Developmental defects included delays in embryo hatching, arrested eye, and shell development, as well as more severe abnormalities such as halted development. Developmental defects induced by some (but not all) synthetic RAR agonists were found to mimic those induced by addition of high concentrations of the natural retinoid isomers. These pharmacological data support a possible physiological role for the RAR in axon guidance and embryonic development of an invertebrate protostome species.