Essential roles for ecdysone signaling during Drosophila mid-embryonic development

Although functions for the steroid hormone ecdysone during Drosophila metamorphosis have been well established, roles for the embryonic ecdysone pulse remain poorly understood. We show that the EcR-USP ecdysone receptor is first activated in the extraembryonic amnioserosa, implicating this tissue as a source of active ecdysteroids in the early embryo. Ecdysone signaling is required for germ band retraction and head involution, morphogenetic movements that shape the first instar larva. This mechanism for coordinating morphogenesis during Drosophila embryonic development parallels the role of ecdysone during metamorphosis. It also provides an intriguing parallel with the role of mammalian extraembryonic tissues as a critical source of steroid hormones during embryonic development.     

Regulation of Drosophila life span by olfaction and food-derived odors

Smell is an ancient sensory system present in organisms from bacteria to humans. In the nematode Caenorhabditis elegans, gustatory and olfactory neurons regulate aging and longevity. Using the fruit fly, Drosophila melanogaster, we showed that exposure to nutrient-derived odorants can modulate life span and partially reverse the longevity-extending effects of dietary restriction. Furthermore, mutation of odorant receptor Or83b resulted in severe olfactory defects, altered adult metabolism, enhanced stress resistance, and extended life span. Our findings indicate that olfaction affects adult physiology and aging in Drosophila, possibly through the perceived availability of nutritional resources, and that olfactory regulation of life span is evolutionarily conserved.     

Regulation of the timing of transposable element excision during maize development

The ability of transposable elements (TEs) to insert into or excise out of a genetic locus can be regulated by genetic, environmental, and developmental factors. Tissue- or organ-specific activity of TEs is a frequent and well-characterized example of spatial, developmental regulation. Regulation of the timing of TE activity during ontogeny is less well understood. To analyze timing, TE-induced variegation was quantified in the aleurone of maize kernels, a tissue composed of only a single layer of cells, and sector sizes were assigned to specific cell divisions in aleurone development. Three TE families, Mu, Spm, and Ac/Ds, were studied at two genetic loci. It was found that the frequency of transposon excision changes drastically (up to 30-fold increase or equivalent decrease) during the proliferation of the aleurone. Moreover, these changes occur at the same cell divisions in all three TE families. These results suggest that the timing of TE excision during maize development can be controlled by the host.     

Regulation of SREBP processing and membrane lipid production by phospholipids in Drosophila

Animal cells exert exquisite control over the physical and chemical properties of their membranes, but the mechanisms are obscure. We show that phosphatidylethanolamine, the major phospholipid in Drosophila, controls the release of sterol regulatory element-binding protein (SREBP) from Drosophila cell membranes, exerting feedback control on the synthesis of fatty acids and phospholipids. The finding that SREBP processing is controlled by different lipids in mammals and flies (sterols and phosphatidylethanolamine, respectively) suggests that an essential function of SREBP is to monitor cell membrane composition and to adjust lipid synthesis accordingly.     

Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase

Paracaspase (MALT1), a member of an evolutionarily conserved superfamily of caspase-like proteins, has been shown to bind and colocalize with the protein Bcl10 in vitro and, because of this association, has been suggested to be involved in the CARMA1-Bcl10 pathway of antigen-induced nuclear factor kappaB (NF-kappaB) activation. We demonstrate that primary T and B lymphocytes from paracaspase-deficient mice are defective in antigen-receptor-induced NF-kappaB activation, cytokine production, and proliferation. Paracaspase acts downstream of Bcl10 to induce NF-kappaB activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the IkappaB kinase complex.     

Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis

Directed cell migration is important for many aspects of normal animal development, but little is known about how cell migrations are guided or the mechanisms by which guidance cues are translated into directed cell movement. Here we present evidence that signaling mediated by the epidermal growth factor receptor (EGFR) guides dorsal migration of border cells during Drosophila oogenesis. The transforming growth factor-alpha (TGF-alpha)-like ligand Gurken appears to serve as the guidance cue. To mediate this guidance function, EGFR signals via a pathway that is independent of Raf-MAP kinase and receptor-specific.     

Regulation of CD8+ T cell development by thymus-specific proteasomes

Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta5t. beta5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta5t into proteasomes in place of beta5 or beta5i selectively reduces this activity. We also found that beta5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.     

Activation of Drosophila Toll during fungal infection by a blood serine protease

Drosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection.     

Malaria parasite development in a Drosophila model

Malaria is a devastating public health menace, killing over one million people every year and infecting about half a billion. Here it is shown that the protozoan Plasmodium gallinaceum, a close relative of the human malaria parasite Plasmodium falciparum, can develop in the fruit fly Drosophila melanogaster. Plasmodium gallinaceum ookinetes injected into the fly developed into sporozoites infectious to the vertebrate host with similar kinetics as seen in the mosquito host Aedes aegypti. In the fly, a component of the insect's innate immune system, the macrophage, can destroy Plasmodia. These experiments suggest that Drosophila can be used as a surrogate mosquito for defining the genetic pathways involved in both vector competence and part of the parasite sexual cycle.     

Ghrelin对绵羊早期体外胚胎发育调节机制的初步研究

【目的】探讨Ghrelin对绵羊早期胚胎发育的调节机制。【方法】将绵羊体外受精早期胚胎在Ghrelin组(300,1 000,10 000ng/mL)、Ghrelin受体拮抗剂D-Lys3-GHRP-6组(10,200,400ng/mL)、D-Lys3-GHRP-6+Ghrelin组(D-Lys3-GHRP-6 400ng/mL,Ghrelin 300,1 000和2 000ng/mL)、空白对照(不加D-Lys3-GHRP-6和Ghrelin)4个组别的胚胎发育液中进行发育培养,采用荧光定量PCR技术分别对各处理不同发育阶段(2-细胞期、4-细胞期、8-细胞期和16-细胞期)绵羊早期胚胎中ERK1、ERK2、P90rsk、Bcl-2、Bax mRNA的表达情况进行检测。【结果】与空白对照组相比,在添加Ghrelin组ERK1、ERK2、P90rsk、Bcl-2基因mRNA的表达表现为显著性上调(P0.05),且这种上调作用可被D-Lys3-GHRP-6所拮抗;在添加Ghrelin组Bax基因mRNA的表达无显著性变化,但在D-Lys3-GHRP-6组Bax基因mRNA的表达表现为显著性上调(P0.05)。【结论】Ghrelin可级联激活MAPK信号通路,抑制促凋亡基因Bax的表达、促进抗凋亡基因Bcl-2的表达,进而促进绵羊早期胚胎的发育。     

Apoptotic force and tissue dynamics during Drosophila embryogenesis

Understanding cell morphogenesis during metazoan development requires knowledge of how cells and the extracellular matrix produce and respond to forces. We investigated how apoptosis, which remodels tissue by eliminating supernumerary cells, also contributes forces to a tissue (the amnioserosa) that promotes cell-sheet fusion (dorsal closure) in the Drosophila embryo. We showed that expression in the amnioserosa of proteins that suppress or enhance apoptosis slows or speeds dorsal closure, respectively. These changes correlate with the forces produced by the amnioserosa and the rate of seam formation between the cell sheets (zipping), key processes that contribute to closure. This apoptotic force is used by the embryo to drive cell-sheet movements during development, a role not classically attributed to apoptosis.     

酒精对生长中果蝇体重的影响

[目的]研究酒精对果蝇生长发育过程中体重的影响。[方法]通过在培养基中加入不同浓度的酒精,并统计F1代的前5d成蛹数目,前5d羽化数目,平均体重以及性别比例,研究不同浓度的酒精对果蝇生长发育过程中体重的影响。[结果]在一定范围内,随着酒精浓度的提高,雄果蝇的体重有逐渐减少的趋势,雌果蝇的体重亦随酒精浓度的增高而减少。酒精对果蝇生长发育有一定的影响,它能够抑制果蝇幼虫和蛹的发育,减轻果蝇的体重,使果蝇的雌雄比例失调。[结论]该研究为酒精对人类的危害提供了参考数据,为孕妇杜绝饮酒和优生优育提供了科学指导。     

Rates of behavior and aging specified by mitochondrial function during development

To explore the role of mitochondrial activity in the aging process, we have lowered the activity of the electron transport chain and adenosine 5'-triphosphate (ATP) synthase with RNA interference (RNAi) in Caenorhabditis elegans. These perturbations reduced body size and behavioral rates and extended adult life-span. Restoring messenger RNA to near-normal levels during adulthood did not elevate ATP levels and did not correct any of these phenotypes. Conversely, inhibiting respiratory-chain components during adulthood only did not reset behavioral rates and did not affect life-span. Thus, the developing animal appears to contain a regulatory system that monitors mitochondrial activity early in life and, in response, establishes rates of respiration, behavior, and aging that persist during adulthood.     

Drosophila Sex lethal gene initiates female development in germline progenitors

Sex determination in the Drosophila germ line is regulated by both the sex of the surrounding soma and cell-autonomous cues. How primordial germ cells (PGCs) initiate sexual development via cell-autonomous mechanisms is unclear. Here, we demonstrate that, in Drosophila, the Sex lethal (Sxl) gene acts autonomously in PGCs to induce female development. Sxl is transiently expressed in PGCs during their migration to the gonads; this expression, which was detected only in XX PGCs, is necessary for PGCs to assume a female fate. Ectopic expression of Sxl in XY PGCs was sufficient to induce them to enter oogenesis and produce functional eggs when transplanted into an XX host. Our data provide powerful evidence that Sxl initiates female germline fate during sexual development.     

Gsα的过表达和缺失对果蝇大脑形态发育的影响

Gsα作为G蛋白复合体的重要组成部分,通过直接调控cAMP-PKA等信号通路参与调控细胞的生命活动。文章通过构建Gsα过量表达及失活突变体,研究Gsα的过量表达及失活对果蝇神经细胞发育的影响。结果表明,在25℃培养条件下,Gsα的过量表达对果蝇幼虫具有致死性。但Gsα的过量表达及失活对果蝇神经细胞的细胞周期和细胞极性没有显著影响。