Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
BMC Genomics ; 22(1): 643, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488624

RESUMO

BACKGROUND: The lower Dipteran fungus fly, Sciara coprophila, has many unique biological features that challenge the rule of genome DNA constancy. For example, Sciara undergoes paternal chromosome elimination and maternal X chromosome nondisjunction during spermatogenesis, paternal X elimination during embryogenesis, intrachromosomal DNA amplification of DNA puff loci during larval development, and germline-limited chromosome elimination from all somatic cells. Paternal chromosome elimination in Sciara was the first observation of imprinting, though the mechanism remains a mystery. Here, we present the first draft genome sequence for Sciara coprophila to take a large step forward in addressing these features. RESULTS: We assembled the Sciara genome using PacBio, Nanopore, and Illumina sequencing. To find an optimal assembly using these datasets, we generated 44 short-read and 50 long-read assemblies. We ranked assemblies using 27 metrics assessing contiguity, gene content, and dataset concordance. The highest-ranking assemblies were scaffolded using BioNano optical maps. RNA-seq datasets from multiple life stages and both sexes facilitated genome annotation. A set of 66 metrics was used to select the first draft assembly for Sciara. Nearly half of the Sciara genome sequence was anchored into chromosomes, and all scaffolds were classified as X-linked or autosomal by coverage. CONCLUSIONS: We determined that X-linked genes in Sciara males undergo dosage compensation. An entire bacterial genome from the Rickettsia genus, a group known to be endosymbionts in insects, was co-assembled with the Sciara genome, opening the possibility that Rickettsia may function in sex determination in Sciara. Finally, the signal level of the PacBio and Nanopore data support the presence of cytosine and adenine modifications in the Sciara genome, consistent with a possible role in imprinting.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Cromossomo X , DNA , Feminino , Fungos , Humanos , Masculino , Análise de Sequência de DNA
2.
Biol Open ; 10(6)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34156079

RESUMO

During oocyte differentiation in mouse fetal ovaries, sister germ cells are connected by intercellular bridges, forming germline cysts. Within the cyst, primary oocytes form via gaining cytoplasm and organelles from sister germ cells through germ cell connectivity. To uncover the role of intercellular bridges in oocyte differentiation, we analyzed mutant female mice lacking testis-expressed 14 (TEX14), a protein involved in intercellular bridge formation and stabilization. In Tex14 homozygous mutant fetal ovaries, germ cells divide to form a reduced number of cysts in which germ cells remained connected via syncytia or fragmented cell membranes, rather than normal intercellular bridges. Compared with wild-type cysts, homozygous mutant cysts fragmented at a higher frequency and produced a greatly reduced number of primary oocytes with precocious cytoplasmic enrichment and enlarged volume. By contrast, Tex14 heterozygous mutant germline cysts were less fragmented and generate primary oocytes at a reduced size. Moreover, enlarged primary oocytes in homozygous mutants were used more efficiently to sustain folliculogenesis than undersized heterozygous mutant primary oocytes. Our observations directly link the nature of fetal germline cysts to oocyte differentiation and development.

3.
Elife ; 92020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32773039

RESUMO

Polycomb silencing represses gene expression and provides a molecular memory of chromatin state that is essential for animal development. We show that Drosophila female germline stem cells (GSCs) provide a powerful system for studying Polycomb silencing. GSCs have a non-canonical distribution of PRC2 activity and lack silenced chromatin like embryonic progenitors. As GSC daughters differentiate into nurse cells and oocytes, nurse cells, like embryonic somatic cells, silence genes in traditional Polycomb domains and in generally inactive chromatin. Developmentally controlled expression of two Polycomb repressive complex 2 (PRC2)-interacting proteins, Pcl and Scm, initiate silencing during differentiation. In GSCs, abundant Pcl inhibits PRC2-dependent silencing globally, while in nurse cells Pcl declines and newly induced Scm concentrates PRC2 activity on traditional Polycomb domains. Our results suggest that PRC2-dependent silencing is developmentally regulated by accessory proteins that either increase the concentration of PRC2 at target sites or inhibit the rate that PRC2 samples chromatin.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Inativação Gênica/fisiologia , Células Germinativas/crescimento & desenvolvimento , Histona-Lisina N-Metiltransferase/genética , Complexo Repressor Polycomb 1/genética , Proteínas do Grupo Polycomb/genética , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Feminino , Histona-Lisina N-Metiltransferase/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Proteínas do Grupo Polycomb/metabolismo
4.
Proc Natl Acad Sci U S A ; 117(33): 20015-20026, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32759216

RESUMO

We sequenced more than 52,500 single cells from embryonic day 11.5 (E11.5) postembryonic day 5 (P5) gonads and performed lineage tracing to analyze primordial follicles and wave 1 medullar follicles during mouse fetal and perinatal oogenesis. Germ cells clustered into six meiotic substages, as well as dying/nurse cells. Wnt-expressing bipotential precursors already present at E11.5 are followed at each developmental stage by two groups of ovarian pregranulosa (PG) cells. One PG group, bipotential pregranulosa (BPG) cells, derives directly from bipotential precursors, expresses Foxl2 early, and associates with cysts throughout the ovary by E12.5. A second PG group, epithelial pregranulosa (EPG) cells, arises in the ovarian surface epithelium, ingresses cortically by E12.5 or earlier, expresses Lgr5, but delays robust Foxl2 expression until after birth. By E19.5, EPG cells predominate in the cortex and differentiate into granulosa cells of quiescent primordial follicles. In contrast, medullar BPG cells differentiate along a distinct pathway to become wave 1 granulosa cells. Reflecting their separate somatic cellular lineages, second wave follicles were ablated by diptheria toxin treatment of Lgr5-DTR-EGFP mice at E16.5 while first wave follicles developed normally and supported fertility. These studies provide insights into ovarian somatic cells and a resource to study the development, physiology, and evolutionary conservation of mammalian ovarian follicles.


Assuntos
Células da Granulosa/citologia , Camundongos/embriologia , Folículo Ovariano/embriologia , Animais , Diferenciação Celular , Linhagem da Célula , Feminino , Proteína Forkhead Box L2/genética , Proteína Forkhead Box L2/metabolismo , Células da Granulosa/metabolismo , Camundongos/metabolismo , Folículo Ovariano/citologia , Folículo Ovariano/metabolismo , Gravidez , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
5.
Elife ; 92020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32175841

RESUMO

Adult Drosophila Malpighian tubules have low rates of cell turnover but are vulnerable to damage caused by stones, like their mammalian counterparts, kidneys. We show that Drosophilarenal stem cells (RSCs) in the ureter and lower tubules comprise a unique, unipotent regenerative compartment. RSCs respond only to loss of nearby principal cells (PCs), cells critical for maintaining ionic balance. Large polyploid PCs are outnumbered by RSCs, which replace each lost cell with multiple PCs of lower ploidy. Notably, RSCs do not replenish principal cells or stellate cells in the upper tubules. RSCs generate daughters by asymmetric Notch signaling, yet RSCs remain quiescent (cell cycle-arrested) without damage. Nevertheless, the capacity for RSC-mediated repair extends the lifespan of flies carrying kidney stones. We propose that abundant, RSC-like stem cells exist in other tissues with low rates of turnover where they may have been mistaken for differentiated tissue cells.


Assuntos
Drosophila melanogaster/fisiologia , Túbulos de Malpighi/citologia , Células-Tronco/fisiologia , Animais , Pontos de Checagem do Ciclo Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Regulação da Expressão Gênica , Genótipo , Cálculos Renais , Transdução de Sinais , Ureter/fisiologia
6.
Elife ; 82019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674908

RESUMO

We previously reported a CRISPR-mediated knock-in strategy into introns of Drosophila genes, generating an attP-FRT-SA-T2A-GAL4-polyA-3XP3-EGFP-FRT-attP transgenic library for multiple uses (Lee et al., 2018a). The method relied on double stranded DNA (dsDNA) homology donors with ~1 kb homology arms. Here, we describe three new simpler ways to edit genes in flies. We create single stranded DNA (ssDNA) donors using PCR and add 100 nt of homology on each side of an integration cassette, followed by enzymatic removal of one strand. Using this method, we generated GFP-tagged proteins that mark organelles in S2 cells. We then describe two dsDNA methods using cheap synthesized donors flanked by 100 nt homology arms and gRNA target sites cloned into a plasmid. Upon injection, donor DNA (1 to 5 kb) is released from the plasmid by Cas9. The cassette integrates efficiently and precisely in vivo. The approach is fast, cheap, and scalable.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Técnicas de Introdução de Genes/métodos , Recombinação Homóloga , Mutagênese Insercional/métodos , Animais , DNA/genética , DNA de Cadeia Simples/genética , Drosophila
7.
Elife ; 82019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755866

RESUMO

Human oocytes frequently generate aneuploid embryos that subsequently miscarry. In contrast, Drosophila oocytes from outbred laboratory stocks develop fully regardless of maternal age. Since mature Drosophila oocytes are not extensively stored in the ovary under laboratory conditions like they are in the wild, we developed a system to investigate how storage affects oocyte quality. The developmental capacity of stored mature Drosophila oocytes decays in a precise manner over 14 days at 25°C. These oocytes are transcriptionally inactive and persist using ongoing translation of stored mRNAs. Ribosome profiling revealed a progressive 2.3-fold decline in average translational efficiency during storage that correlates with oocyte functional decay. Although normal bipolar meiotic spindles predominate during the first week, oocytes stored for longer periods increasingly show tripolar, monopolar and other spindle defects, and give rise to embryos that fail to develop due to aneuploidy. Thus, meiotic chromosome segregation in mature Drosophila oocytes is uniquely sensitive to prolonged storage. Our work suggests the chromosome instability of human embryos could be mitigated by reducing the period of time mature human oocytes are stored in the ovary prior to ovulation.


Assuntos
Drosophila/fisiologia , Oócitos/fisiologia , Oogênese/fisiologia , Ovário/fisiologia , Fuso Acromático/fisiologia , Envelhecimento , Aneuploidia , Animais , Segregação de Cromossomos , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , RNA Mensageiro/metabolismo , Ribossomos , Temperatura
8.
Dev Cell ; 47(1): 98-111.e5, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30220569

RESUMO

Tissue homeostasis involves a complex balance of developmental signals and environmental cues that dictate stem cell function. We found that dietary lipids control enteroendocrine cell production from Drosophila posterior midgut stem cells. Dietary cholesterol influences new intestinal cell differentiation in an Hr96-dependent manner by altering the level and duration of Notch signaling. Exogenous lipids modulate Delta ligand and Notch extracellular domain stability and alter their trafficking in endosomal vesicles. Lipid-modulated Notch signaling occurs in other nutrient-dependent tissues, suggesting that Delta trafficking in many cells is sensitive to cellular sterol levels. These diet-mediated alterations in young animals contribute to a metabolic program that persists after the diet changes. A low-sterol diet also slows the proliferation of enteroendocrine tumors initiated by Notch pathway disruption. Thus, a specific dietary nutrient can modify a key intercellular signaling pathway to shift stem cell differentiation and cause lasting changes in tissue structure and physiology.


Assuntos
Colesterol na Dieta/efeitos adversos , Lipídeos/fisiologia , Receptores Notch/efeitos dos fármacos , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Colesterol/metabolismo , Colesterol na Dieta/metabolismo , Proteínas de Drosophila/efeitos dos fármacos , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Enterócitos/metabolismo , Células Enteroendócrinas/efeitos dos fármacos , Células Enteroendócrinas/fisiologia , Intestinos/citologia , Peptídeos e Proteínas de Sinalização Intracelular , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Proteínas de Membrana , Receptores Notch/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/citologia , Esteróis/metabolismo
9.
Science ; 361(6403): 709-712, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30115809

RESUMO

Mutations in the fragile X mental retardation 1 gene (FMR1) cause the most common inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA) translation, but identifying functional targets has been difficult. We analyzed quiescent Drosophila oocytes, which, like neural synapses, depend heavily on translating stored mRNA. Ribosome profiling revealed that FMR1 enhances rather than represses the translation of mRNAs that overlap previously identified FMR1 targets, and acts preferentially on large proteins. Human homologs of at least 20 targets are associated with dominant intellectual disability, and 30 others with recessive neurodevelopmental dysfunction. Stored oocytes lacking FMR1 usually generate embryos with severe neural defects, unlike stored wild-type oocytes, which suggests that translation of multiple large proteins by stored mRNAs is defective in fragile X syndrome and possibly other autism spectrum disorders.


Assuntos
Transtorno Autístico/metabolismo , Proteínas de Drosophila/fisiologia , Proteína do X Frágil de Retardo Mental/fisiologia , Malformações do Sistema Nervoso/genética , Biossíntese de Proteínas , Animais , Transtorno Autístico/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Embrião não Mamífero/anormalidades , Proteína do X Frágil de Retardo Mental/genética , Técnicas de Silenciamento de Genes , Humanos , Oócitos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
10.
Genetics ; 209(2): 381-387, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29669732

RESUMO

Controlling the expression of genes using a binary system involving the yeast GAL4 transcription factor has been a mainstay of Drosophila developmental genetics for nearly 30 years. However, most existing GAL4 expression constructs only function effectively in somatic cells, but not in germ cells during oogenesis, for unknown reasons. A special upstream activation sequence (UAS) promoter, UASp was created that does express during oogenesis, but the need to use different constructs for somatic and female germline cells has remained a significant technical limitation. Here, we show that the expression problem of UASt and many other Drosophila molecular tools in germline cells is caused by their core Hsp70 promoter sequences, which are targeted in female germ cells by Hsp70-directed Piwi-interacting RNAs (piRNAs) generated from endogenous Hsp70 gene sequences. In a genetic background lacking genomic Hsp70 genes and associated piRNAs, UASt-based constructs function effectively during oogenesis. By reducing Hsp70 sequences targeted by piRNAs, we created UASz, which functions better than UASp in the germline and like UASt in somatic cells.


Assuntos
Proteínas de Choque Térmico HSP72/genética , Oócitos/metabolismo , Regiões Promotoras Genéticas , RNA Interferente Pequeno/genética , Ativação Transcricional , Animais , Drosophila/genética , Feminino , Proteínas de Choque Térmico HSP72/metabolismo , Interferência de RNA
11.
Elife ; 72018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29565247

RESUMO

We generated a library of ~1000 Drosophila stocks in which we inserted a construct in the intron of genes allowing expression of GAL4 under control of endogenous promoters while arresting transcription with a polyadenylation signal 3' of the GAL4. This allows numerous applications. First, ~90% of insertions in essential genes cause a severe loss-of-function phenotype, an effective way to mutagenize genes. Interestingly, 12/14 chromosomes engineered through CRISPR do not carry second-site lethal mutations. Second, 26/36 (70%) of lethal insertions tested are rescued with a single UAS-cDNA construct. Third, loss-of-function phenotypes associated with many GAL4 insertions can be reverted by excision with UAS-flippase. Fourth, GAL4 driven UAS-GFP/RFP reports tissue and cell-type specificity of gene expression with high sensitivity. We report the expression of hundreds of genes not previously reported. Finally, inserted cassettes can be replaced with GFP or any DNA. These stocks comprise a powerful resource for assessing gene function.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Biblioteca Gênica , Fatores de Transcrição/genética , Animais , Animais Geneticamente Modificados , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Perfilação da Expressão Gênica , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mutagênese Insercional , Especificidade de Órgãos/genética , Fatores de Transcrição/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-29167281

RESUMO

Polytene chromosomes have for 80 years provided the highest resolution view of interphase genome structure in an animal cell nucleus. These chromosomes represent the normal genomic state of nearly all Drosophila larval and many adult cells, and a better understanding of their striking banded structure has been sought for decades. A more recently appreciated characteristic of Drosophila polytene cells is somatic genome instability caused by unfinished replication (UR). Repair of stalled forks generates enough deletions in polytene salivary gland cells to alter 10%-90% of the DNA strands within more than 100 UR regions comprising 20% of the euchromatic genome. We accurately map UR regions and show that most approximate large polytene bands, indicating that replication forks frequently stall near band boundaries in late S phase. Chromosome conformation capture has recently identified dense topologically associated domains (TADs) in many genomes and most UR bands are similar or slightly smaller than a cognate Drosophila TAD. We argue that bands serve the evolutionarily ancient function of coordinating genome replication with local gene activity. We also discuss the relatively recent evolution of polyteny and somatic instability in Diptera and propose that these processes helped propel the amazing success of two-winged flies in becoming the most ecologically diverse insect group, with 200 times the number of species as mammals.

13.
Curr Opin Genet Dev ; 45: 58-68, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28347941

RESUMO

During development, cells adopt distinct metabolic strategies to support growth, produce energy, and meet the demands of a mature tissue. Some of these metabolic states maintain a constrained program of nutrient utilization, while others providing metabolic flexibility as a means to couple developmental progression with nutrient availability. Here we discuss our understanding of metabolic programs, and how they support specific aspects of animal development. During phases of rapid proliferation a subset of metabolic programs provide the building blocks to support growth. During differentiation, metabolic programs shift to support the unique demands of each tissue. Finally, we discuss how a model system, such as Drosophila egg development, can provide a versatile platform to discover novel mechanisms controlling programmed shift in metabolism.


Assuntos
Diferenciação Celular/genética , Proliferação de Células , Drosophila/metabolismo , Metabolismo , Animais , Metabolismo Energético , Feminino , Hepatócitos/metabolismo , Humanos , Síndrome Metabólica/metabolismo , Neurônios/metabolismo , Oogênese/fisiologia
14.
G3 (Bethesda) ; 7(1): 309-318, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-27866148

RESUMO

The Drosophila melanogaster ovarian follicle cell lineage provides a powerful system for investigating how epigenetic changes contribute to differentiation. Downstream from an epithelial stem cell, follicle progenitors undergo nine mitotic cell cycles before transitioning to the endocycle and initiating differentiation. During their proliferative phase, follicle progenitors experience Lsd1-dependent changes in epigenetic stability that can be monitored using GAL4::UAS variegation. Eventually, follicle progenitors acquire competence to respond to Delta, a Notch ligand present in the environment, which signals them to cease division and initiate differentiation. The time required to acquire competence determines the duration of mitotic cycling and hence the final number of follicle cells. We carried out a screen for dominant modifiers of variegation spanning nearly 70% of Drosophila euchromatin to identify new genes influencing follicle progenitor epigenetic maturation. The eight genes found include chromatin modifiers, but also cell cycle regulators and transcription factors. Five of the modifier genes accelerate the acquisition of progenitor competence and reduce follicle cell number, however, the other three genes affect follicle cell number in an unexpected manner.


Assuntos
Drosophila melanogaster/genética , Oogênese/genética , Folículo Ovariano/crescimento & desenvolvimento , Receptores Notch/genética , Fatores de Transcrição/genética , Animais , Diferenciação Celular/genética , Linhagem da Célula/genética , Proteínas de Drosophila/genética , Epigênese Genética , Eucromatina/genética , Feminino , Mitose/genética , Folículo Ovariano/metabolismo , Oxirredutases N-Desmetilantes/genética , Células-Tronco
15.
Methods Mol Biol ; 1463: 125-138, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27734353

RESUMO

Lineage analysis is widely used because it provides a very powerful tool for characterizing the developmental behavior of the cells in vivo. In this chapter, we describe a particularly informative variant of lineage analysis that we term "single-cell lineage analysis". As in traditional lineage analysis, the method employs a Tamoxifen (Tmx)-inducible CAGCreER mouse line, which is crossed to an R26R reporter line that can be activated by Cre-mediated DNA recombination. However, instead of driving CreER at a high level within a subset of cells defined by a particular promoter, CreER is driven with a generic promoter that is active in essentially all cells throughout the lifespan of the mouse. Specificity comes from using only a very low dose of Tmx so that just a few random, widely separated individual cells undergo recombination and become labeled. The growth and behavior of most such initially marked cells can subsequently be followed over time because each one forms a growing clone of marked cells that does not overlap with other clones due to their rarity. Following individual cell growth patterns provides much more information than can be derived from traditional lineage analysis, which relies on promoter specificity and uses high doses of Tmx that cannot resolve the behavior of single cells. We illustrate the value of single-cell lineage analysis using a recent study of fetal germ cell development and a recent search for female germ-line stem cells in adult mouse ovaries.


Assuntos
Células Germinativas/citologia , Oócitos/citologia , Oogênese , Análise de Célula Única/métodos , Animais , Diferenciação Celular , Linhagem da Célula , Feminino , Genes Reporter , Células Germinativas/metabolismo , Camundongos , Oócitos/metabolismo , Regiões Promotoras Genéticas
17.
PLoS One ; 11(3): e0151251, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26958853

RESUMO

Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues.


Assuntos
Proteínas de Drosophila/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Distrofias Hereditárias da Córnea/metabolismo , Modelos Animais de Doenças , Drosophila , Endotélio Corneano/metabolismo , Feminino , Mamíferos , Camundongos , Camundongos Mutantes , Poliploidia , Fator de Transcrição AP-1/metabolismo
18.
Curr Top Dev Biol ; 117: 405-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26969992

RESUMO

Biological research has a realistic chance within the next 50 years of discovering the basic mechanisms by which metazoan genomes encode the complex morphological structures and capabilities that characterize life as we know it. However, achieving those goals is now threatened by researchers who advocate an end to basic research on nonmammalian organisms. For the sake of society, medicine, and the science of biology, the focus of biomedical research should place more emphasis on basic studies guided by the underlying evolutionary commonality of all major animals, as manifested in their genes, pathways, cells, and organs.


Assuntos
Evolução Biológica , Embriologia/tendências , Animais , Embriologia/história , História do Século XX , História do Século XXI , Humanos
19.
Science ; 352(6281): 95-9, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26917595

RESUMO

Oocytes differentiate in diverse species by receiving organelles and cytoplasm from sister germ cells while joined in germline cysts or syncytia. Mouse primordial germ cells form germline cysts, but the role of cysts in oogenesis is unknown. We find that mouse germ cells receive organelles from neighboring cyst cells and build a Balbiani body to become oocytes, whereas nurselike germ cells die. Organelle movement, Balbiani body formation, and oocyte fate determination are selectively blocked by low levels of microtubule-dependent transport inhibitors. Membrane breakdown within the cyst and an apoptosis-like process are associated with organelle transfer into the oocyte, events reminiscent of nurse cell dumping in Drosophila We propose that cytoplasmic and organelle transport plays an evolutionarily conserved and functionally important role in mammalian oocyte differentiation.


Assuntos
Células Gigantes/citologia , Oócitos/citologia , Oogênese , Organelas/fisiologia , Animais , Apoptose , Evolução Biológica , Citoplasma/fisiologia , Citoplasma/ultraestrutura , Feminino , Camundongos , Microtúbulos/efeitos dos fármacos , Microtúbulos/fisiologia
20.
Cell ; 164(3): 420-32, 2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26824655

RESUMO

Reproduction is heavily influenced by nutrition and metabolic state. Many common reproductive disorders in humans are associated with diabetes and metabolic syndrome. We characterized the metabolic mechanisms that support oogenesis and found that mitochondria in mature Drosophila oocytes enter a low-activity state of respiratory quiescence by remodeling the electron transport chain (ETC). This shift in mitochondrial function leads to extensive glycogen accumulation late in oogenesis and is required for the developmental competence of the oocyte. Decreased insulin signaling initiates ETC remodeling and mitochondrial respiratory quiescence through glycogen synthase kinase 3 (GSK3). Intriguingly, we observed similar ETC remodeling and glycogen uptake in maturing Xenopus oocytes, suggesting that these processes are evolutionarily conserved aspects of oocyte development. Our studies reveal an important link between metabolism and oocyte maturation.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio/metabolismo , Oogênese , Xenopus laevis/embriologia , Animais , Drosophila melanogaster/metabolismo , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário , Feminino , Fatores de Transcrição Forkhead/metabolismo , Mitocôndrias/metabolismo , Proteína Oncogênica v-akt/metabolismo , Oócitos/citologia , Oócitos/metabolismo , Xenopus laevis/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...