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Author: Elizabeth Danielle Larson Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
During the early stages of development, the fertilized germ cells are rapidly reprogrammed to form a pluripotent embryo. This transition in cell fate is coordinated by pioneer transcription factors that have the ability to open inaccessible chromatin to allow other factors to bind and drive gene expression. As chromatin is known to pose a barrier to transcription factor binding, these unique properties of pioneer factors make them instrumental in driving gene-regulatory networks that control critical developmental transitions. Despite the ability to access closed chromatin, pioneer factors do not function the same throughout development, so it is crucial that we understand how specific cellular environments influence pioneer factor binding and activity. The pioneer transcription factor Zelda (Zld) is essential for early embryonic reprogramming in Drosophila melanogaster. Research has shown that Zld shapes the chromatin and transcriptional landscape in the early embryo, but Zld's role later in development and the mechanisms by which Zld was regulated remained unclear. Our data has demonstrated that Zld functions to maintain the undifferentiated state of a neural stem cell population in the developing larval brain. Additionally, the ability of Zld to reprogram is conserved as Zld can also reprogram in the larval neural stem cell lineage. However, Zld binding is redistributed in the larval neuroblasts from the early embryo indicating that developmental context shapes where this transcription factor can bind. We show that Zld levels have to be precisely regulated in both the brain and the early embryo as misexpression of Zld at either stage is detrimental to the animal. The protein Brain Tumor (Brat) regulates Zld levels at both stages of development and we demonstrate that in embryos lacking functional Brat, Zld is prematurely expressed. However, early Zld expression is not sufficient to precociously activate the zygotic genome. Thus, expression of a genomic activator must be coordinated with timing of the division cycles in order to properly activate the genome. Together, our data demonstrate the Zld must be tightly regulated throughout development in order to allow for rapid transitions in cell fate. Together, our studies will help us better understand the transcriptional and post-transcriptional mechanisms regulating pioneer transcription factors.
Author: Elizabeth Danielle Larson Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
During the early stages of development, the fertilized germ cells are rapidly reprogrammed to form a pluripotent embryo. This transition in cell fate is coordinated by pioneer transcription factors that have the ability to open inaccessible chromatin to allow other factors to bind and drive gene expression. As chromatin is known to pose a barrier to transcription factor binding, these unique properties of pioneer factors make them instrumental in driving gene-regulatory networks that control critical developmental transitions. Despite the ability to access closed chromatin, pioneer factors do not function the same throughout development, so it is crucial that we understand how specific cellular environments influence pioneer factor binding and activity. The pioneer transcription factor Zelda (Zld) is essential for early embryonic reprogramming in Drosophila melanogaster. Research has shown that Zld shapes the chromatin and transcriptional landscape in the early embryo, but Zld's role later in development and the mechanisms by which Zld was regulated remained unclear. Our data has demonstrated that Zld functions to maintain the undifferentiated state of a neural stem cell population in the developing larval brain. Additionally, the ability of Zld to reprogram is conserved as Zld can also reprogram in the larval neural stem cell lineage. However, Zld binding is redistributed in the larval neuroblasts from the early embryo indicating that developmental context shapes where this transcription factor can bind. We show that Zld levels have to be precisely regulated in both the brain and the early embryo as misexpression of Zld at either stage is detrimental to the animal. The protein Brain Tumor (Brat) regulates Zld levels at both stages of development and we demonstrate that in embryos lacking functional Brat, Zld is prematurely expressed. However, early Zld expression is not sufficient to precociously activate the zygotic genome. Thus, expression of a genomic activator must be coordinated with timing of the division cycles in order to properly activate the genome. Together, our data demonstrate the Zld must be tightly regulated throughout development in order to allow for rapid transitions in cell fate. Together, our studies will help us better understand the transcriptional and post-transcriptional mechanisms regulating pioneer transcription factors.
Author: Elizabeth Danielle Larson Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
During the early stages of development, the fertilized germ cells are rapidly reprogrammed to form a pluripotent embryo. This transition in cell fate is coordinated by pioneer transcription factors that have the ability to open inaccessible chromatin to allow other factors to bind and drive gene expression. As chromatin is known to pose a barrier to transcription factor binding, these unique properties of pioneer factors make them instrumental in driving gene-regulatory networks that control critical developmental transitions. Despite the ability to access closed chromatin, pioneer factors do not function the same throughout development, so it is crucial that we understand how specific cellular environments influence pioneer factor binding and activity. The pioneer transcription factor Zelda (Zld) is essential for early embryonic reprogramming in Drosophila melanogaster. Research has shown that Zld shapes the chromatin and transcriptional landscape in the early embryo, but Zld's role later in development and the mechanisms by which Zld was regulated remained unclear. Our data has demonstrated that Zld functions to maintain the undifferentiated state of a neural stem cell population in the developing larval brain. Additionally, the ability of Zld to reprogram is conserved as Zld can also reprogram in the larval neural stem cell lineage. However, Zld binding is redistributed in the larval neuroblasts from the early embryo indicating that developmental context shapes where this transcription factor can bind. We show that Zld levels have to be precisely regulated in both the brain and the early embryo as misexpression of Zld at either stage is detrimental to the animal. The protein Brain Tumor (Brat) regulates Zld levels at both stages of development and we demonstrate that in embryos lacking functional Brat, Zld is prematurely expressed. However, early Zld expression is not sufficient to precociously activate the zygotic genome. Thus, expression of a genomic activator must be coordinated with timing of the division cycles in order to properly activate the genome. Together, our data demonstrate the Zld must be tightly regulated throughout development in order to allow for rapid transitions in cell fate. Together, our studies will help us better understand the transcriptional and post-transcriptional mechanisms regulating pioneer transcription factors.
Author: Stephanie Yee Publisher: ISBN: Category : Languages : en Pages :
Book Description
"Post-transcriptional control is a critical determinant of gene expression that acts at the level of the messenger RNA (mRNA), which includes processes such as translational control and RNA localization, and is the focus of this thesis. This regulation is in part dictated by the characteristics of the 5’ and 3’ untranslated regions (UTRs) of the mRNA and the cis-elements they harbour. Translational control can occur at the initiation step where the 5’ cap structure of the mRNA is recognized by the eIF4E, whose activity can be modulated by the eIF4E-binding protein (4E-BP), a repressor of translation. The target of rapamycin (TOR) pathway integrates a plethora of signals and impinges on protein synthesis through its action on 4E-BPs and S6 kinases (S6Ks), two well-characterized targets. The TOR/4E-BP/eIF4E axis is known to regulate the translation of subsets of mRNAs with distinct features in their 5’UTRs. In light of recent work that demonstrated dysregulated translation of specific mRNAs in the brains of mice lacking 4E-BP2 and engendering autism spectrum disorder-like phenotypes, we endeavoured to similarly identify mRNAs regulated by d4E-BP in Drosophila. In Chapter 2, we performed ribosome profiling to identify specific mRNAs that are translationally regulated downstream of d4E-BP in the adult fly head, used as a proxy for the brain. Gene ontology (GO) analysis revealed that the corresponding genes of some of the upregulated mRNAs are involved in innate immunity. We determined that upregulated mRNAs possess 5’UTRs that are shorter but more complex. In our effort to validate one of the targets, dS6K, we detected elevated levels of p-RPS6, a readout of dS6K activity, in d4E-BPnull flies. We conclude there are subsets of differentially ribosome-associated mRNAs with distinct 5’UTR features in the d4E-BPnull fly head.Subcellular localization of mRNAs in the Drosophila embryo establishes a molecular asymmetry of maternally-inherited determinants that is essential for its development. Of the hundreds of transcripts that localize to the primordial germ cells at the posterior of the early embryo, only 55 RNAs accumulate around posterior nuclei prior to the development of those cells, termed RNA islands. Many of the genes that encode these mRNAs have established functions in embryonic patterning and germline development. Despite their common destination to RNA islands, a shared localization element has yet to be identified. In Chapter 3, we mapped the localization elements within the 3’UTRs of two transcripts that localize to RNA islands, polar granule component (pgc) and germ cell-less (gcl). Based on deletion mutation analysis, we report that gcl has redundant localization elements, while pgc possesses a localization element in the distal region. We show that the localization of polar granule proteins, Oskar, Tudor and Vasa, and 11 RNAs have conserved posterior localization in Drosophilids. Using recent findings of a sequence motif that contributes to RNA island localization, we found that this motif is enriched in the 3’UTRs of the majority of transcripts that localize in this way. Our data suggests that the RNA island type of posterior localization is an important process for directing the localization of transcripts with key roles in germline development, as highlighted by the many aspects of this process that is conserved"--
Author: Publisher: Academic Press ISBN: 012386500X Category : Science Languages : en Pages : 387
Book Description
This new volume in the Current Topics in Developmental Biology series concentrates on transcriptional switches during development. It includes chapters on such topics as muscle diversity, transcriptional response to genome structural variation, and the temporal gene network in Drosophila neural stem cells. With an international team of authors, this volume is a must-have addition for researchers and students alike. Concentrates on transcriptional switches during development Includes chapters on such topics as muscle diversity, transcriptional response to genome structural variation, and the temporal gene network in Drosophila neural stem cells With an international team of authors, this volume is a must-have addition for researchers and students alike
Author: Steven Walter Miller Publisher: ISBN: 9781109280043 Category : Languages : en Pages : 274
Book Description
Molecular and genetic studies over the past two decades have established that animals ranging from the fruit fly to the human utilize a common "toolkit" of genes to create the myriad cell types during development. For even some of the most well studied developmental paradigms, however, little is known of the transcriptional regulatory networks activated by these core components. Moreover, how these networks manifest the initial cell fate decision remains a rigorous topic of investigation. The Drosophila melanogaster mechanosensory organ lineage has long been a model for binary cell fate specification mechanisms. While it is well-established that the Notch signaling pathway is the dominant cell fate specification mechanism in this lineage, little is known of the battery of genes downstream of the canonical pathway components that enforce the cell fate decision. In this body of work I analyze the Notch signaling events at opposite ends of the lineage with the specification of the mechanosensory organ precursor cell (SOP) at the beginning and the post-mitotic socket and shaft cells at the penultimate of the lineage. These studies focus on the transcriptional regulation of three genes, neuralized, Sox15 and sv. I utilize a number of loss of function mutants, misexpression studies, and transgenic reporter constructs to identify enhancer modules and tease out their regulatory factors. Chapter 2 comprises an analysis of the transcriptional regulation of neuralized during SOP specification where I present evidence that neuralized is both a participant in and a target of Notch signaling, requiring two partially redundant. Chapter 3 focuses on the transcriptional regulation and function of Sox15, a transcription factor specifically expressed in the post-mitotic socket cell. I show that Sox15 is a target of Notch signaling in the socket cell and is required for the proper differentiation of the socket cell as it relates to mechanosensory function. Chapter 4 dovetails off Sox15 and examines regulation of sv in the shaft cell, where I find the dominant theme is auto-regulation. Lastly, Chapter 5 describes the development of a new transgenic reporter system I developed for the rapid screening of genomic fragments for enhancer activity.
Author: Markus Alan Nevil Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
During development transcription factors coordinate complex gene regulatory networks to drive changes in cell fate. These essential regulators have been characterized in a number of cellular and developmental contexts, yet the mechanisms by which they potentiate changes in transcription largely remain unclear. To further our understanding of how these factors function, I have studied a highly conserved factor that initiates cell fate changes during development. In metazoans, the specification of epithelial cells is an essential process that leads to the formation of a number of tissues in the adult. Additionally, the maintenance of these cell types is essential for survival and prevention of disease. The highly conserved Grainy head (GRH) family of transcription factors are master regulators of epithelial morphogenesis and cell fate. Despite its ubiquity and importance, the gene regulatory network controlled by this factor and the mechanisms by which it controls this network during development initially remained unknown. In this dissertation, I outline our evidence of how GRH shapes Drosophila development from early embryogenesis into larval development and suggest mechanisms by which this is achieved. In Chapter 1, I begin by introducing the eukaryotic chromatin landscape and the factors which influence it, including the conserved GRH family. Chapter 2 contains published work that elucidates the gene regulatory network that is controlled by the GRH during Drosophila embryonic and larval development. Notably, we identified the surprisingly stable binding of GRH that ultimately is not predictive of its requirement for proper gene expression. In Chapter 3, I present unpublished work that uncovered the temporal regulation of GRH pioneering activity at cis-regulatory modules.
Author: Marissa Marie Gaskill Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
For cellular identity to be established during reprogramming events certain regions of the genome need to be activated while others are silenced. In several organisms, transcription factors have been identified that drive widespread transcriptional programs capable of determining cell fate. Many of these factors have non-uniform distribution in the nucleus. Aggregation of factors into subnuclear domains has been suggested to be important for transcriptional regulation and three-dimensional (3D) organization of chromatin within the nucleus. However, the functional relevance of these domains has not been robustly tested. To further our understanding of how transcription factors reprogram the genome during development, I have studied the role of GAGA Factor (GAF) during the highly conserved reprogramming event known as the maternal-to-zygotic transition (MZT) in Drosophila. Prior to our work it was known that the factor Zelda (Zld) broadly activates the Drosophila genome and promotes chromatin accessibility during the MZT, however it was uncertain whether additional factors were required. We demonstrated that GAF functions along with Zld to activate the zygotic genome and promote chromatin accessibility during the MZT. Furthermore, we characterized the GAF subnuclear foci that form during the MZT to probe how organization into subnuclear domains contributes to the function of transcription factors. We discovered that GAF foci are pericentric satellite repeats. Unlike most factors that depend on multivalent interactions of intrinsically disordered regions to promote aggregation, GAF localization to foci is driven by DNA binding activity. At these regions, GAF is required for transcriptional repression and heterochromatin formation. Therefore, GAF has opposing roles in transcriptional regulation in diffuse populations compared to foci. Together, our data demonstrate that GAF functions to reprogram both the active and silent genome during the MZT. These findings provide insight into how multiple pioneer factors function together to activate the genome, and also how subnuclear organization contributes to discrete functions in transcription regulation at different regions of the genome.
Author: Dipak K. Dube Publisher: Springer Science & Business Media ISBN: 9780817642266 Category : Science Languages : en Pages : 304
Book Description
Myofibrillogenesis has been studied extensively over the last 100 years. Until recently, we have not had a comprehensive understanding of this fundamental process. The emergence of new technologies in molecular and cellular biology, combined with classical embryology, have started to unravel some of the complexities of myofibril assembly in striated muscles. In striated muscles, the contractile proteins are arranged in a highly ordered three dimensional lattice known as the sarcomere. The assembly of a myofibril involves the precise ordering of several proteins into a linear array of sarcomeres. Multiple isoforms in many of these proteins further complicate the process, making it difficult to define the precise role of each component. This volume has been compiled as a comprehensive reference on myofibrillogenesis. In addition, the book includes reviews on myofibrillar disarray under various pathological conditions, such as familial hypertrophic cardiomyopathy (FHC), and incorporates a section on the conduction system in the heart. Much of the information in this volume has not been described elsewhere. Presented in a manner to be of value to students and teachers alike, "Myofibrillogenesis" will be an invaluable reference source for all in the fields of muscle biology and heart development.
Author: Werner A. Mueller Publisher: Springer ISBN: 3662437848 Category : Science Languages : en Pages : 723
Book Description
This book describes human development including sexual reproduction and stem cell research with the development of model organisms that are accessible to genetic and experimental analysis in readily understandable texts and 315 multi-colored graphics. The introductory account of model organisms selected from the entire animal kingdom presents general principles, which are then outlined in subsequent chapters devoted to, for example, sexual development; genes controlling development and their contemporary molecular-analysis methods; production of clones and transgenic animals; development of the nervous and circulatory systems; regenerative medicine and ageing. Finally the evolution of developmental toolkits and novelties is discussed including the genetic basis of the enlargement of the human forebrain. Separate boxes are devoted to controversial questions such as the benefits and problems of prenatal diagnostics or the construction of ancient body plans.
Author: Elizabeth Danielle Larson
Author: Elizabeth Danielle Larson
Author: Elizabeth Danielle Larson
Author: Stephanie Yee
Author: 
Author: Steven Walter Miller
Author: Markus Alan Nevil
Author: Marissa Marie Gaskill
Author: Xuemin Lu
Author: Dipak K. Dube
Author: Werner A. Mueller