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1.
Genes Dev ; 31(14): 1494-1508, 2017 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-28838946

RESUMEN

The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica , Sitios Genéticos , Histonas/genética , Animales , Secuencia de Bases , Cromatina/metabolismo , Secuencia Conservada , ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Histonas/metabolismo , Regiones Promotoras Genéticas , Secuencias Repetitivas de Ácidos Nucleicos , Factores de Transcripción/metabolismo
2.
Development ; 146(23)2019 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-31748204

RESUMEN

During central nervous system development, spatiotemporal gene expression programs mediate specific lineage decisions to generate neuronal and glial cell types from neural stem cells (NSCs). However, little is known about the epigenetic landscape underlying these highly complex developmental events. Here, we perform ChIP-seq on distinct subtypes of Drosophila FACS-purified NSCs and their differentiated progeny to dissect the epigenetic changes accompanying the major lineage decisions in vivo By analyzing active and repressive histone modifications, we show that stem cell identity genes are silenced during differentiation by loss of their activating marks and not via repressive histone modifications. Our analysis also uncovers a new set of genes specifically required for altering lineage patterns in type II neuroblasts (NBs), one of the two main Drosophila NSC identities. Finally, we demonstrate that this subtype specification in NBs, unlike NSC differentiation, requires Polycomb-group-mediated repression.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Proteínas de Drosophila/metabolismo , Histonas/metabolismo , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Células-Madre Neurales/metabolismo , Procesamiento Proteico-Postraduccional , Animales , Neoplasias Encefálicas/patología , Drosophila melanogaster , Células Madre Neoplásicas/patología , Células-Madre Neurales/patología
3.
Nature ; 512(7515): 449-52, 2014 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-25164756

RESUMEN

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.


Asunto(s)
Caenorhabditis elegans/citología , Caenorhabditis elegans/genética , Cromatina/genética , Cromatina/metabolismo , Drosophila melanogaster/citología , Drosophila melanogaster/genética , Animales , Línea Celular , Centrómero/genética , Centrómero/metabolismo , Cromatina/química , Ensamble y Desensamble de Cromatina/genética , Replicación del ADN/genética , Elementos de Facilitación Genéticos/genética , Epigénesis Genética , Heterocromatina/química , Heterocromatina/genética , Heterocromatina/metabolismo , Histonas/química , Histonas/metabolismo , Humanos , Anotación de Secuencia Molecular , Lámina Nuclear/metabolismo , Nucleosomas/química , Nucleosomas/genética , Nucleosomas/metabolismo , Regiones Promotoras Genéticas/genética , Especificidad de la Especie
4.
Nature ; 504(7480): 465-469, 2013 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-24162848

RESUMEN

The Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation (XCI), the process by which mammals compensate for unequal numbers of sex chromosomes. During XCI, Xist coats the future inactive X chromosome (Xi) and recruits Polycomb repressive complex 2 (PRC2) to the X-inactivation centre (Xic). How Xist spreads silencing on a 150-megabases scale is unclear. Here we generate high-resolution maps of Xist binding on the X chromosome across a developmental time course using CHART-seq. In female cells undergoing XCI de novo, Xist follows a two-step mechanism, initially targeting gene-rich islands before spreading to intervening gene-poor domains. Xist is depleted from genes that escape XCI but may concentrate near escapee boundaries. Xist binding is linearly proportional to PRC2 density and H3 lysine 27 trimethylation (H3K27me3), indicating co-migration of Xist and PRC2. Interestingly, when Xist is acutely stripped off from the Xi in post-XCI cells, Xist recovers quickly within both gene-rich and gene-poor domains on a timescale of hours instead of days, indicating a previously primed Xi chromatin state. We conclude that Xist spreading takes distinct stage-specific forms. During initial establishment, Xist follows a two-step mechanism, but during maintenance, Xist spreads rapidly to both gene-rich and gene-poor regions.


Asunto(s)
ARN Largo no Codificante/metabolismo , Inactivación del Cromosoma X , Cromosoma X/metabolismo , Animales , Cromatina/genética , Cromatina/metabolismo , Células Madre Embrionarias/metabolismo , Femenino , Fibroblastos/metabolismo , Silenciador del Gen , Genes , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/química , Histonas/metabolismo , Lisina/metabolismo , Metilación , Ratones , Modelos Genéticos , ARN Largo no Codificante/genética , Cromosoma X/genética , Inactivación del Cromosoma X/genética
5.
BMC Genomics ; 17(1): 816, 2016 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-27769162

RESUMEN

BACKGROUND: ChIP-seq is the primary technique used to investigate genome-wide protein-DNA interactions. As part of this procedure, immunoprecipitated DNA must undergo "library preparation" to enable subsequent high-throughput sequencing. To facilitate the analysis of biopsy samples and rare cell populations, there has been a recent proliferation of methods allowing sequencing library preparation from low-input DNA amounts. However, little information exists on the relative merits, performance, comparability and biases inherent to these procedures. Notably, recently developed single-cell ChIP procedures employing microfluidics must also employ library preparation reagents to allow downstream sequencing. RESULTS: In this study, seven methods designed for low-input DNA/ChIP-seq sample preparation (Accel-NGS® 2S, Bowman-method, HTML-PCR, SeqPlex™, DNA SMART™, TELP and ThruPLEX®) were performed on five replicates of 1 ng and 0.1 ng input H3K4me3 ChIP material, and compared to a "gold standard" reference PCR-free dataset. The performance of each method was examined for the prevalence of unmappable reads, amplification-derived duplicate reads, reproducibility, and for the sensitivity and specificity of peak calling. CONCLUSIONS: We identified consistent high performance in a subset of the tested reagents, which should aid researchers in choosing the most appropriate reagents for their studies. Furthermore, we expect this work to drive future advances by identifying and encouraging use of the most promising methods and reagents. The results may also aid judgements on how comparable are existing datasets that have been prepared with different sample library preparation reagents.


Asunto(s)
Inmunoprecipitación de Cromatina , Biblioteca de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Inmunoprecipitación de Cromatina/métodos , Mapeo Cromosómico , Genoma , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN
6.
Genomics ; 106(3): 140-144, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26079656

RESUMEN

Enhancers work with promoters to refine the timing, location, and level of gene expression. As they perform these functions, active enhancers generate a chromatin environment that is distinct from other areas of the genome. Therefore, profiling enhancer-associated chromatin features can produce genome-wide maps of potential regulatory elements. This review focuses on current technologies used to produce maps of potential tissue-specific enhancers by profiling chromatin from primary tissue. First, cells are separated from whole organisms either by affinity purification, automated cell sorting, or microdissection. Isolating the tissue prior to analysis ensures that the molecular signature of active enhancers will not become lost in an averaged signal from unrelated cell types. After cell isolation, the molecular feature that is profiled will depend on the abundance and quality of the harvested material. The combination of tissue isolation plus genome-wide chromatin profiling has successfully identified enhancers in several pioneering studies. In the future, the regulatory apparatus of healthy and diseased tissues will be explored in this manner, as researchers use the combined techniques to gain insight into how active enhancers may influence disease progression.


Asunto(s)
Cromatina/genética , Elementos de Facilitación Genéticos , Genoma Humano , Mapeo Cromosómico , Humanos , Especificidad de Órganos/genética
7.
BMC Genomics ; 14: 466, 2013 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-23837789

RESUMEN

BACKGROUND: High throughput sequencing is frequently used to discover the location of regulatory interactions on chromatin. However, techniques that enrich DNA where regulatory activity takes place, such as chromatin immunoprecipitation (ChIP), often yield less DNA than optimal for sequencing library preparation. Existing protocols for picogram-scale libraries require concomitant fragmentation of DNA, pre-amplification, or long overnight steps. RESULTS: We report a simple and fast library construction method that produces libraries from sub-nanogram quantities of DNA. This protocol yields conventional libraries with barcodes suitable for multiplexed sample analysis on the Illumina platform. We demonstrate the utility of this method by constructing a ChIP-seq library from 100 pg of ChIP DNA that demonstrates equivalent genomic coverage of target regions to a library produced from a larger scale experiment. CONCLUSIONS: Application of this method allows whole genome studies from samples where material or yields are limiting.


Asunto(s)
ADN/genética , Biblioteca de Genes , Análisis de Secuencia de ADN/métodos , Inmunoprecipitación de Cromatina , Factores de Tiempo
8.
Nat Cell Biol ; 7(11): 1099-105, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16228011

RESUMEN

Heterotrimeric G proteins act during signal transduction in response to extracellular ligands. They are also required for spindle orientation and cell polarity during asymmetric cell division. We show here that, in Drosophila, both functions require the Galpha interaction partner Ric-8. Drosophila Ric-8 is a cytoplasmic protein that binds both the GDP- and GTP-bound form of the G-protein alpha-subunit Galphai. In ric-8 mutants, neither Galphai nor its associated beta-subunit Gbeta13F are localized at the plasma membrane, which leads to their degradation in the cytosol. During asymmetric cell division, this leads to various defects: apico-basal polarity is not maintained, mitotic spindles are misoriented and the size of the two daughter cells becomes nearly equal. ric-8 mutants also have defects in gastrulation that resemble mutants in the Galpha protein concertina or the extracellular ligand foldedgastrulation. Our results indicate a model in which both receptor-dependent and receptor-independent G-protein functions are executed at the plasma membrane and require the Ric-8 protein.


Asunto(s)
División Celular/fisiología , Membrana Celular/metabolismo , Proteínas de Drosophila/fisiología , Drosophila/fisiología , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Factor de Crecimiento Transformador beta/fisiología , Animales , Animales Modificados Genéticamente , Polaridad Celular , Drosophila/embriología , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Subunidades beta de la Proteína de Unión al GTP/metabolismo , Factores de Intercambio de Guanina Nucleótido/fisiología , Proteínas de Unión al GTP Heterotriméricas/genética , Neuronas/metabolismo , Neuronas/fisiología , Neuronas/ultraestructura
9.
Dev Cell ; 10(6): 731-42, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16740476

RESUMEN

During asymmetric cell division, the mitotic spindle must be properly oriented to ensure the asymmetric segregation of cell fate determinants into only one of the two daughter cells. In Drosophila neuroblasts, spindle orientation requires heterotrimeric G proteins and the G alpha binding partner Pins, but how the Pins-G alphai complex interacts with the mitotic spindle is unclear. Here, we show that Pins binds directly to the microtubule binding protein Mud, the Drosophila homolog of NuMA. Like NuMA, Mud can bind to microtubules and enhance microtubule polymerization. In the absence of Mud, mitotic spindles in Drosophila neuroblasts fail to align with the polarity axis. This can lead to symmetric segregation of the cell fate determinants Brat and Prospero, resulting in the mis-specification of daughter cell fates and tumor-like over proliferation in the Drosophila nervous system. Our data suggest a model in which asymmetrically localized Pins-G alphai complexes regulate spindle orientation by directly binding to Mud.


Asunto(s)
Antígenos Nucleares/metabolismo , Polaridad Celular , Proteínas de Drosophila/metabolismo , Drosophila/genética , Proteínas de Insectos/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas Asociadas a Matriz Nuclear/metabolismo , Huso Acromático/fisiología , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Antígenos Nucleares/química , Antígenos Nucleares/genética , Antígenos Nucleares/fisiología , Sitios de Unión , Proteínas de Ciclo Celular , División Celular , Secuencia Conservada , Drosophila/citología , Drosophila/embriología , Drosophila/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiología , Embrión no Mamífero , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Inhibidores de Disociación de Guanina Nucleótido/química , Inhibidores de Disociación de Guanina Nucleótido/metabolismo , Proteínas de Insectos/genética , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Microtúbulos/metabolismo , Modelos Biológicos , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/fisiología , Neuronas/citología , Neuronas/metabolismo , Proteínas Asociadas a Matriz Nuclear/química , Proteínas Asociadas a Matriz Nuclear/genética , Proteínas Asociadas a Matriz Nuclear/fisiología , Filogenia , Unión Proteica , Estructura Terciaria de Proteína
10.
Curr Protoc Mol Biol ; 119: 7.30.1-7.30.24, 2017 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-28678441

RESUMEN

Next-generation sequencing (NGS) is a powerful tool for genomic studies, translational research, and clinical diagnostics that enables the detection of single nucleotide polymorphisms, insertions and deletions, copy number variations, and other genetic variations. Target enrichment technologies improve the efficiency of NGS by only sequencing regions of interest, which reduces sequencing costs while increasing coverage of the selected targets. Here we present NEBNext Direct® , a hybridization-based, target-enrichment approach that addresses many of the shortcomings of traditional target-enrichment methods. This approach features a simple, 7-hr workflow that uses enzymatic removal of off-target sequences to achieve a high specificity for regions of interest. Additionally, unique molecular identifiers are incorporated for the identification and filtering of PCR duplicates. The same protocol can be used across a wide range of input amounts, input types, and panel sizes, enabling NEBNext Direct to be broadly applicable across a wide variety of research and diagnostic needs. © 2017 by John Wiley & Sons, Inc.


Asunto(s)
Biblioteca de Genes , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Hibridación de Ácido Nucleico/métodos , Factores de Tiempo
11.
Nat Commun ; 7: 11485, 2016 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-27151365

RESUMEN

Chromatin accessibility plays a fundamental role in gene regulation. Nucleosome placement, usually measured by quantifying protection of DNA from enzymatic digestion, can regulate accessibility. We introduce a metric that uses micrococcal nuclease (MNase) digestion in a novel manner to measure chromatin accessibility by combining information from several digests of increasing depths. This metric, MACC (MNase accessibility), quantifies the inherent heterogeneity of nucleosome accessibility in which some nucleosomes are seen preferentially at high MNase and some at low MNase. MACC interrogates each genomic locus, measuring both nucleosome location and accessibility in the same assay. MACC can be performed either with or without a histone immunoprecipitation step, and thereby compares histone and non-histone protection. We find that changes in accessibility at enhancers, promoters and other regulatory regions do not correlate with changes in nucleosome occupancy. Moreover, high nucleosome occupancy does not necessarily preclude high accessibility, which reveals novel principles of chromatin regulation.


Asunto(s)
Cromatina/metabolismo , Nucleasa Microcócica , Nucleosomas/metabolismo , Animales , Línea Celular , Drosophila melanogaster , Regulación de la Expresión Génica , Histonas/metabolismo , Humanos , Células K562 , Ratones , Células Madre Embrionarias de Ratones , Células-Madre Neurales , Regiones Promotoras Genéticas , Análisis de Secuencia de ARN
12.
Elife ; 3: e02833, 2014 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-25082344

RESUMEN

The bithorax complex (BX-C) in Drosophila melanogaster is a cluster of homeotic genes that determine body segment identity. Expression of these genes is governed by cis-regulatory domains, one for each parasegment. Stable repression of these domains depends on Polycomb Group (PcG) functions, which include trimethylation of lysine 27 of histone H3 (H3K27me3). To search for parasegment-specific signatures that reflect PcG function, chromatin from single parasegments was isolated and profiled. The H3K27me3 profiles across the BX-C in successive parasegments showed a 'stairstep' pattern that revealed sharp boundaries of the BX-C regulatory domains. Acetylated H3K27 was broadly enriched across active domains, in a pattern complementary to H3K27me3. The CCCTC-binding protein (CTCF) bound the borders between H3K27 modification domains; it was retained even in parasegments where adjacent domains lack H3K27me3. These findings provide a molecular definition of the homeotic domains, and implicate precisely positioned H3K27 modifications as a central determinant of segment identity.


Asunto(s)
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Epigénesis Genética , Genes Homeobox , Histonas/genética , Complejo Represivo Polycomb 1/genética , Proteínas Represoras/genética , Acetilación , Animales , Tipificación del Cuerpo/genética , Factor de Unión a CCCTC , Cromatina/química , Cromatina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Embrión no Mamífero , Femenino , Regulación del Desarrollo de la Expresión Génica , Histonas/metabolismo , Lisina/metabolismo , Masculino , Complejo Represivo Polycomb 1/metabolismo , Unión Proteica , Proteínas Represoras/metabolismo , Transducción de Señal
13.
Nat Cell Biol ; 15(5): 491-501, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23604319

RESUMEN

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Ensamble y Desensamble de Cromatina , Longevidad , Factores de Transcripción/metabolismo , Adaptación Fisiológica , Animales , Sitios de Unión , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Cromatografía en Gel , Escherichia coli/genética , Escherichia coli/metabolismo , Factores de Transcripción Forkhead , Regulación de la Expresión Génica , Estimación de Kaplan-Meier , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Motivos de Nucleótidos , Estrés Oxidativo , Regiones Promotoras Genéticas , Unión Proteica , Interferencia de ARN , Factores de Transcripción/genética , Activación Transcripcional
14.
Dev Cell ; 14(4): 535-46, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18342578

RESUMEN

In both vertebrates and insects, neurons typically arise from neural stem cells or terminally dividing intermediate progenitors. Here, we describe another mode of neurogenesis where neural stem cells generate secondary precursors that undergo multiple rounds of self-renewing transit-amplifying divisions. We identify the Posterior Asense-Negative (PAN) neuroblasts, which do not express the transcription factors Asense or Prospero. PAN neuroblasts rely on the segregating determinants Numb and Brat to generate smaller, secondary neuroblasts that in turn give rise to ganglion mother cells (GMCs) and neurons throughout larval development. In brat or numb mutants, misspecified secondary neuroblasts are unable to produce differentiated progeny and initiate tumor-like overgrowth. In prospero mutants, however, tumors arise from GMCs while secondary neuroblasts are correctly specified. Our data describe a transit-amplifying lineage in the Drosophila nervous system and suggest that different vulnerabilities in intermediate cell types can affect the outcome of tumor suppressor loss in stem cell lineages.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Genes Supresores de Tumor , Hormonas Juveniles/metabolismo , Neuronas/fisiología , Células Madre/fisiología , Animales , Encéfalo/citología , Encéfalo/embriología , Encéfalo/metabolismo , Ciclo Celular/fisiología , Diferenciación Celular , Linaje de la Célula , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/citología , Drosophila melanogaster/embriología , Drosophila melanogaster/metabolismo , Regulación del Desarrollo de la Expresión Génica , Hormonas Juveniles/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/citología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal/fisiología , Células Madre/citología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
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