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At least 721 records · Page 40Linked to original sources

PubMed2004

Maternal and environmental factors in early cloned embryo development.

Cloning by somatic cell nuclear transfer (SCNT) in mammals has revealed the remarkable ability of an oocyte to reprogram somatic cell nuclei and induce them to recapitulate the developmental program. Despite the success, cloning remains very inefficient. This review summarizes recent observations from cloning in mice that reveal some of the likely causes for the present inefficiency. One cause appears to be the slow pace of reprogramming combined with the early onset of genome transcription, which together cause cloned embryos to elaborate many somatic cell characteristics even before the first cleavage division. The altered phenotypes of cloned embryos render standard embryo culture conditions grossly sub-optimum. Another cause appears to be a hitherto unappreciated contribution of spindle-associated factors to early embryo development. As current procedures remove the spindle and associated factors, cloned embryos lack these factors. These observations are providing new insight into basic mammalian embryology. They also reveal possible changes to protocols that could improve the overall success of cloning.

Animals↗

PubMed2001

The Drosophila sex determination hierarchy modulates wingless and decapentaplegic signaling to deploy dachshund sex-specifically in the genital imaginal disc.

The integration of multiple developmental cues is crucial to the combinatorial strategies for cell specification that underlie metazoan development. In the Drosophila genital imaginal disc, which gives rise to the sexually dimorphic genitalia and analia, sexual identity must be integrated with positional cues, in order to direct the appropriate sexually dimorphic developmental program. Sex determination in Drosophila is controlled by a hierarchy of regulatory genes. The last known gene in the somatic branch of this hierarchy is the transcription factor doublesex (dsx); however, targets of the hierarchy that play a role in sexually dimorphic development have remained elusive. We show that the gene dachshund (dac) is differentially expressed in the male and female genital discs, and plays sex-specific roles in the development of the genitalia. Furthermore, the sex determination hierarchy mediates this sex-specific deployment of dac by modulating the regulation of dac by the pattern formation genes wingless (wg) and decapentaplegic (dpp). We find that the sex determination pathway acts cell-autonomously to determine whether dac is activated by wg signaling, as in females, or by dpp signaling, as in males.

Animals↗

PubMed2003

Buffy, a Drosophila Bcl-2 protein, has anti-apoptotic and cell cycle inhibitory functions.

Bcl-2 family proteins are key regulators of apoptosis. Both pro-apoptotic and anti-apoptotic members of this family are found in mammalian cells, but only the pro-apoptotic protein Debcl has been characterized in Drosophila: Here we report that Buffy, the second Drosophila Bcl-2-like protein, is a pro-survival protein. Ablation of Buffy by RNA interference leads to ectopic apoptosis, whereas overexpression of buffy results in the inhibition of developmental programmed cell death and gamma irradiation-induced apoptosis. Buffy interacts genetically and physically with Debcl to suppress Debcl-induced cell death. Genetic interactions suggest that Buffy acts downstream of Rpr, Grim and Hid, and upstream of the apical caspase Dronc. Furthermore, overexpression of buffy inhibits ectopic cell death in diap1 (th(5)) mutants. Taken together these data suggest that Buffy can act downstream of Rpr, Grim and Hid to block caspase-dependent cell death. Overexpression of Buffy in the embryo results in inhibition of the cell cycle, consistent with a G(1)/early-S phase arrest. Our data suggest that Buffy is functionally similar to the mammalian pro-survival Bcl-2 family of proteins.

Amino Acid Motifs↗

PubMed2006

Computational and experimental analysis identifies Arabidopsis genes specifically expressed during early seed development.

BACKGROUND: Plant seeds are complex organs in which maternal tissues, embryo and endosperm, follow distinct but coordinated developmental programs. Some morphogenetic and metabolic processes are exclusively associated with seed development. The goal of this study was to explore the feasibility of incorporating the available online bioinformatics databases to discover Arabidopsis genes specifically expressed in certain organs, in our case immature seeds. RESULTS: A total of 11,032 EST sequences obtained from isolated immature seeds were used as the initial dataset (178 of them newly described here). A pilot study was performed using EST virtual subtraction followed by microarray data analysis, using the Genevestigator tool. These techniques led to the identification of 49 immature seed-specific genes. The findings were validated by RT-PCR analysis and in situ hybridization. CONCLUSION: We conclude that the combined in silico data analysis is an effective data mining strategy for the identification of tissue-specific gene expression.

Arabidopsis↗

PubMed2000

Involvement of the glucose-regulated protein 94 (Dd-GRP94) in starvation response of Dictyostelium discoideum cells.

Upon deprivation of nutrients, Dictyostelium discoideum Ax-2 cells arrest proliferation and initiate a metamorphosed developmental program including induction of altered gene expressions which are necessary for differentiation. In Ax-2 cells, we found out a member of Hsp90 family usually contained in the endoplasmic reticulum (ER), Dd-GRP94 (Dictyostelium discoideum glucose-regulated protein 94). In general, GRP94 are induced either by glucose-depletion or by depletion of Ca(2+) in intracellular Ca(2+) stores. Unexpectedly, however, the expression of Dd-grp94 was greatly reduced within 60 min of starvation. Dd-grp94-overexpressing cells (GRP94(OE) cells) collected without forming distinct aggregation streams, and never formed normal fruiting bodies. Also, prespore differentiation as well as maturation into spores and stalk cells were particularly impaired in the GRP94(OE) cells. Thus Dd-GRP94 seems to be crucial in late differentiation as well as in starvation response.

Amino Acids↗

PubMed2006

A novel nuclear-localized CCCH-type zinc finger protein, OsDOS, is involved in delaying leaf senescence in rice.

Leaf senescence is a developmentally programmed degeneration process, which is fine tuned by a complex regulatory network for plant fitness. However, molecular regulation of leaf senescence is poorly understood, especially in rice (Oryza sativa), an important staple crop for more than half of the world population. Here, we report a novel nuclear-localized CCCH-type zinc finger protein, Oryza sativa delay of the onset of senescence (OsDOS), involved in delaying leaf senescence in rice. The expression of OsDOS was down-regulated during natural leaf senescence, panicle development, and pollination, although its transcripts were accumulated in various organs. RNAi knockdown of OsDOS caused an accelerated age-dependent leaf senescence, whereas its overexpression produced a marked delay of leaf senescence, suggesting that it acts as a negative regulator for leaf senescence. A genome-wide expression analysis further confirmed its negative regulation for leaf senescence and revealed that, in particular, the jasmonate (JA) pathway was found to be hyperactive in the OsDOS RNAi transgenic lines but impaired in the OsDOS overexpressing transgenic lines, indicating that this pathway is likely involved in the OsDOS-mediated delaying of leaf senescence. Furthermore, methyl JA treatments of both seeds and detached leaves from the RNAi and the overexpressing transgenic lines showed hyper- and hyporesponses, respectively, consistent with the negative regulation of the JA pathway by OsDOS. Together, these results indicate that OsDOS is a novel nuclear protein that delays leaf senescence likely, at least in part, by integrating developmental cues to the JA pathway.

Amino Acid Sequence↗

PubMed1999

Fertilization and wounding of the style induce the expression of a highly conserved plant gene homologous to a Plasmodium falciparum surface antigen in the wild potato Solanum chacoense Bitt.

Pistil tissues are actively involved in pollen tube growth and respond to the presence of the growing pollen tubes by modulating the expression of specific genes. Once fertilization has occurred, complex developmental programs lead to embryogenesis, ovary maturation, and seed set. In order to understand the early events that follow pollination and fertilization we have used a subtractive hybridization approach to characterize genes which are related to pollination and fertilization events. One cDNA clone isolated and named SPP30 (Solanum pollinated pistil) was found to share significant sequence identities with a Plasmodium falciparum (malaria parasite) surface antigen and a yeast gene of unknown function. Searches in recent EST databases also revealed that SPP30 homologues are found in both monocot and dicot species. The presence of this conserved gene in evolutionarily distant organisms such as yeast, Plasmodium, and plants suggests that it codes for an essential cellular function. This is also strengthened by its extremely high sequence conservation in both monocots and dicots where virtually all substitutions tolerated are conservative.

Amino Acid Sequence↗

PubMed2004

An arginine-histone methyltransferase, CARMER, coordinates ecdysone-mediated apoptosis in Drosophila cells.

Developmentally programmed cell death is regulated by a balance between pro- and anti-death signaling. During Drosophila metamorphosis, the removal of larval tissues is dependent on the steroid hormone ecdysone, which controls the levels of pro- and anti-death molecules. Ecdysone binds to its heterodimeric receptor ecdysone receptor/ultraspiracle to mediate transcription of primary response genes. Here we show that CARMER, an arginine-histone methyltransferase, is critical in coordinating ecdysone-induced expression of Drosophila cell death genes. Ablation of CARMER blocks ecdysone-induced cell death in Drosophila cells, but not apoptosis induced by cell stress. We demonstrate that CARMER associates with the ecdysone receptor complex and modulates the ecdysone-induced transcription of a number of apoptotic genes. Thus, the chromatin-modifying protein, CARMER, modulates cell death by controlling the hormone-dependent expression of the core cell death machinery.

Amino Acid Sequence↗

PubMed2000

Adrenal tumorigenesis targeted by the corticotropin-regulated promoter of the aldo-keto reductase AKR1B7 gene in transgenic mice.

Studies of ACTH functions in adrenal steroidogenesis have been facilitated by the availability of immortalized mouse adrenocortical Y1 cells. In order to obtain alternative cell lines with a more differentiated zona fasciculata (ZF) phenotype we used targeted tumorigenesis strategy. We have generated transgenic mice expressing the SV40 T antigen under the control of the ACTH-dependent promoter for the AKR1B7/MVDP gene (aldo-keto reductase 1B7/mouse vas deferens protein), which encodes an enzyme responsible for detoxifying isocaproaldehyde, the product of side-chain cleavage of cholesterol generated by steroidogenesis. Our previous data indicated that in the mouse adrenal, AKR1B7 expression was restricted to the ZF and that a 0.5-kb promoter region was able to target specific adrenal expression in transgenic mice. In situ hybridization analyses indicate that AKR1B7 expression during fetal and post-natal periods paralleled the onset of glucocorticoid synthesis and the development of ZF. In transgenic mice, ACTH control and developmental programming of the CAT gene driven by the 0.5-kb promoter followed endogenous gene regulation. Then transgenic mice harboring the 0.5-kb/SV40 T antigen construct were generated and two founders out of three developed adrenal tumors. Cells derived from the tumor of founder 1 (ATC1) were grown in presence of forskolin to maintain ACTH receptor expression and were tested for ACTH responsiveness by immunocychemistry and northern blot analyses. Even after several passages, the ACTH induced AKR1B7 and P450c11beta mRNAs accumulations were similar to that observed in mouse primary adrenocortical cell cultures. Our findings suggest that ATC1 cells have conserved essential features of ZF cells. In order to achieve complete characterization of these cells further analyses are currently performed to investigate their steroidogenic activity.

Adrenal Gland Neoplasms↗

PubMed2007

The expression pattern of nuclear receptors during cerebellar development.

The cerebellum is essential for fine control of movement and posture, and it has been a useful model for studying many aspects of neural development because of its relatively simple anatomy and developmental program. However, the roles of nuclear receptors (NRs) underlying formation of the cerebellum and maintenance of cerebellar functions are still poorly characterized. As a contribution to the Nuclear Receptor Signaling Atlas (NURSA), we employed immunohistochemistry to investigate the expression pattern of 18 NRs in the cerebellum. Ten receptors were demonstrated to be expressed in the postnatal day 21 (P21) cerebellum. Among them, five receptors (COUP-TFI, COUP-TFII, RORalpha, ERbeta, and ERRgamma) were expressed at all stages (embryonic stage, P0, P7, and P21) examined. Interestingly, COUP-TFI and COUP-TFII show differential anterior-posterior expression patterns during cerebellar development. Taken together, our results suggest that members of the nuclear receptor superfamily might play importantly physiological roles in the cerebellum.

Animals↗

PubMed2001

Transcription factors that regulate growth and differentiation of myeloid cells.

Recently much progress has been made in our understanding of how myeloid progenitor cells undergo commitment and become mature granulocytes or monocytes/macrophages. Studies of normal and leukemic myeloid cells as well as those of cells derived from mice with targeted disruption showed that a series of transcription factors play a major role in both commitment and maturation of myeloid cells. This is primarily because these transcription factors direct an ordered pattern of gene expression according to a well-defined developmental program. PU.1, an Ets family member, is one of the master transcription factors identified to regulate development of both granulocytes and monocytes/macrophages. Further, C/EBPalpha and C/EBPvarepsilon of the bZip family have important roles in directing granulocytic maturation. A number of additional transcription factors such as AML1, RARalpha, MZF-1, Hox and STAT families of transcription factors, Egr-1 and c-myb etc are shown to play roles in myeloid cell differentiation. Our laboratory has recently obtained evidence that ICSBP, a member of the IRF family, is involved in lineage commitment during myeloid cell differentiation and stimulates maturation of functional macrophages. Future elucidation of pathways and networks through which these transcription factors act in various stages of development would provide a more definitive picture of myeloid cell commitment and maturation.

Animals↗

PubMed2004

Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans.

Studies using the nematode Caenorhabditis elegans as a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling pathway in the regulation of organismal longevity through its action on a subset of target genes. These targets can be classified into genes that shorten or extend life-span upon their induction. Genes that shorten life-span include a variety of stress response genes, among them genes encoding catalases; however, no evidence directly implicates catalases in the aging process of nematodes or other organisms. Using genetic mutants, we show that lack of peroxisomal catalase CTL-2 causes a progeric phenotype in C. elegans. Lack of peroxisomal catalase also affects the developmental program of C. elegans, since Deltactl-2 mutants exhibit decreased egg laying capacity. In contrast, lack of cytosolic catalase CTL-1 has no effect on either nematode aging or egg laying capacity. The Deltactl-2 mutation also shortens the maximum life-span of the long lived Deltaclk-1 mutant and accelerates the onset of its egg laying period. The more rapid aging of Deltactl-2 worms is apparently not due to increased carbonylation of the major C. elegans proteins, although altered peroxisome morphology in the Deltactl-2 mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Deltactl-2 mutant. Our findings support an important role for peroxisomal catalase in both the development and aging of C. elegans and suggest the utility of the Deltactl-2 mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia.

Aging↗

PubMed2005

Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation.

Compelling epidemiological and experimental evidence indicates that a suboptimal environment during fetal and neonatal development in both humans and animals may programme offspring susceptibility to later development of several chronic diseases including obesity and diabetes in which altered carbohydrate metabolism plays a central role. One of the most interesting and significant features of developmental programming is the evidence from several studies that the adverse consequences of altered intrauterine environments can be passed transgenerationally from mother (F0) to daughter (F1) to second generation offspring (F2). We determined whether when F0 female rats are exposed to protein restriction during pregnancy and/or lactation their F1 female pups deliver F2 offspring with in vivo evidence of altered glucose and insulin metabolism. We fed F0 virgin Wistar rats a normal control 20% casein diet (C) or a protein restricted isocaloric diet (R) containing 10% casein during pregnancy. F1 female R pups weighed less than C at birth. After delivery, mothers received C or R diet during lactation to provide four F1 offspring groups CC (first letter pregnancy diet and second lactation diet), RR, CR and RC. All F1 female offspring were fed ad libitum with C diet after weaning and during their first pregnancy and lactation. As they grew female offspring (F1) of RR and CR mothers exhibited low body weight and food intake with increased sensitivity to insulin during a glucose tolerance test at 110 days of postnatal life. Male F2 CR offspring showed evidence of insulin resistance. In contrast RC F2 females showed evidence of insulin resistance. Sex differences were also observed in F2 offspring in resting glucose and insulin and insulin: glucose ratios. These sex differences also showed differences specific to stage of development time window. We conclude that maternal protein restriction adversely affects glucose and insulin metabolism of male and female F2 offspring in a manner specific to sex and developmental time window during their mother's (the F1) fetal and neonatal development.

Animals↗

PubMed2007

Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling.

The urogenital and reproductive organs, including the external genitalia, bladder and urethra, develop as anatomically aligned organs. Descriptive and experimental embryology suggest that the cloaca, and its derivative, the urogenital sinus, contribute to the formation of these organs. However, it is unknown how the primary tissue lineages in, and adjacent to, the cloaca give rise to the above organs, nor is bladder formation understood. While it is known that sonic hedgehog (Shh) is expressed by the cloacal epithelia, the developmental programs that regulate and coordinate the formation of the urogenital and reproductive organs have not been elucidated. Here we report that Shh mutant embryos display hypoplasia of external genitalia, internal urethra (pelvic urethra) and bladder. The importance of Shh signaling in the development of bladder and external genitalia was confirmed by analyzing a variety of mutant mouse lines with defective hedgehog signaling. By genetically labeling hedgehog-responding tissue lineages adjacent to the cloaca and urogenital sinus, we defined the contribution of these tissues to the bladder and external genitalia. We discovered that development of smooth muscle myosin-positive embryonic bladder mesenchyme requires Shh signaling, and that the bladder mesenchyme and dorsal (upper) external genitalia derive from Shh-responsive peri-cloacal mesenchyme. Thus, the mesenchymal precursors for multiple urogenital structures derive from peri-cloacal mesenchyme and the coordination of urogenital organ formation from these precursors is orchestrated by Shh signals.

Animals↗

PubMed2002

Control of developmental timing by small temporal RNAs: a paradigm for RNA-mediated regulation of gene expression.

Heterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin-4 and let-7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post-transcriptional regulation by binding to complementary sequences in the 3' untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1 and members of the RDE-1/AGO1 family of proteins, which are better known for their roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin-4 and let-7. We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms.

3' Untranslated Regions↗

PubMed2003

Selective regulation of xSlo splice variants during Xenopus embryogenesis.

Calcium-activated potassium channels regulate excitability of the adult nervous system. In contrast, little is known about the contribution of calcium-activated potassium channels to excitability of the embryonic nervous system when electrical membrane properties and intracellular calcium levels show dramatic changes. Embryonic Xenopus spinal neurons exhibit a well-characterized developmental program of excitability that involves several different currents including calcium-activated ones. Here, we show that a molecular determinant of calcium-activated potassium channels, xSlo, is expressed during Xenopus embryogenesis even prior to differentiation of excitable tissues. Five different xSlo variants are expressed in embryonic tissues as a consequence of alternative exon usage at a single splice site. One of these variants, xSlo59, is neural-specific, and its expression is limited to late stages of neuronal differentiation. However, expression of the four other variants occurs in both muscle and neurons at all stages of development examined. Electrophysiological analysis of recombinant xSlo channels reveals that the xSlo59 exon serves as a gain-of-function module and allows physiologically relevant levels of membrane potential and intracellular calcium to activate effectively the resultant channel. These results suggest that xSlo59 channels play a unique role in sculpting the excitable membrane properties of Xenopus spinal neurons.

Action Potentials↗

PubMed2003

Tbx1 is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer.

Haploinsufficiency of Tbx1 is likely a major determinant of cardiac and craniofacial birth defects associated with DiGeorge syndrome. Although mice deficient in Tbx1 exhibit pharyngeal and aortic arch defects, the developmental program and mechanisms through which Tbx1 functions are relatively unknown. We identified a single cis-element upstream of Tbx1 that recognized winged helix/forkhead box (Fox)-containing transcription factors and was essential for regulation of Tbx1 transcription in the pharyngeal endoderm and head mesenchyme. The Tbx1 regulatory region was responsive to signaling by Sonic hedgehog (Shh) in vivo. We show that Shh is necessary for aortic arch development, similar to Tbx1, and is also required for expression of Foxa2 and Foxc2 in the pharyngeal endoderm and head mesenchyme, respectively. Foxa2, Foxc1, or Foxc2 could bind and activate transcription through the critical cis-element upstream of Tbx1, and Foxc proteins were required, within their expression domains, for Tbx1 transcription in vivo. We propose that Tbx1 is a direct transcriptional target of Fox proteins and that Fox proteins may serve an intermediary role in Shh regulation of Tbx1.

Animals↗

PubMed2000

Tissue- and stage-specific modulation of Wingless signaling by the segment polarity gene lines.

Wnt signaling controls a variety of developmental programs but the mechanisms by which the same signal leads to distinct outputs remain unclear. To address this question, we identified stage-specific modulators of Wingless (Wg) signaling in the Drosophila embryonic epidermis. We show that lines (lin) is essential for Wg-dependent patterning in dorsal epidermis. lin encodes a novel protein that acts cell-autonomously, downstream or in parallel to Armadillo (Arm) and upstream of Wg-dependent target genes. Lin can accumulate in nuclei of cells signaled by Wg, suggesting that signaling promotes entry of Lin into the nucleus, where it cooperates with Arm and Pangolin. Thus, a stage-specific modulator is used to mediate Wg signaling activity in dorsal patterning. Hedgehog (Hh) controls half of the parasegmental pattern dorsally and antagonizes Wg function to do so. Lin can accumulate in the cytoplasm of cells signaled by Hh, suggesting that Hh antagonizes Wg function by prohibiting Lin from entering the nucleus.

Animals↗