Genetic Analysis of Signaling Pathways Involved in Drosophila Embryonic Axon Guidance PDF Download
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Author: Jessica Elizabeth Palmer
Publisher:
ISBN:
Category :
Languages : en
Pages : 294
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Author: Jessica Elizabeth Palmer
Publisher:
ISBN:
Category :
Languages : en
Pages : 294
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Author: Huidy Shu
Publisher:
ISBN:
Category :
Languages : en
Pages : 336
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Author: Janice L. Fritz
Publisher:
ISBN:
Category :
Languages : en
Pages : 288
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Author: Vicki L. McGovern
Publisher:
ISBN:
Category : Axons
Languages : en
Pages :
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Abstract: The goal of developmental neurobiology is to understand how a complex nervous system is wired. During development of the central nervous system (CNS) neural connections are assembled in a highly stereotyped fashion. How do axons find their targets with such accuracy? We know that axon migration is direct by attractive and repulsive guidance cues located in the extracellular environment. While many guidance molecules have been identified, we are only just beginning to understand the mechanisms of axon guidance. In order to identify additional genes involved in axon guidance and CNS development we performed a misexpression screen. Using P-elements and the UAS/GAL4 system, transcription of endogenous genes was induced in the embryonic CNS. Misexpression phenotypes were then identified immunohistochemically with two monoclonal antibodies: BP102, a general axon marker, and 1D4, which labels a subset of axon pathways. Over 4100 individual P-element insertion lines were screened. Twenty-five insertions corresponding to 18 genes resulted in misexpression phenotypes. Genes involved in axon guidance, embryonic patterning, and cell cycle regulation were identified. Several transcription factors that have not been previously implicated in CNS development were isolated and characterized as well. The identification of these transcription factors is intriguing since little is known about the transcriptional regulation of axon guidance genes. Additionally, we have studied the regulation of the previously identified guidance molecule Commissureless (Comm). Comm is necessary for proper axon guidance at the CNS midline of the Drosophila embryo. In the absence of Comm, commissural axons fail to cross the midline and instead make ispilateral projections on their respective sides of the midline. Using mosaic analysis, we have identified a cell autonomous neuronal requirement for Comm. Clones containing mutant alleles of comm formed commissural projections at a statistically significant reduced frequency when compared to wild type clones. This result suggests that regulation of Comm expression in neurons is critical for Comm's function in axon guidance at the CNS midline. These studies have both advanced the understanding of the regulation of Comm, and have identified new potential regulators of guidance molecules.
Author: David J. Forsthoefel
Publisher:
ISBN:
Category : Actin
Languages : en
Pages :
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Abstract: The Drosophila melanogaster embryo is an ideal system in which to study axon guidance, because of the relative simplicity of the nervous system and the evolutionary conservation of the molecules utilized during development. The Abelson cytoplasmic tyrosine kinase regulates actin cytoskeletal dynamics in Drosophila, mice, and humans. In Drosophila, Abl is expressed in the developing central and peripheral nervous systems (CNS and PNS). In a genetic screen for modifiers of the Abl mutant semilethality phenotype, we identified trio, a cytoplasmic guanine nucleotide exchange factor that is also expressed in the CNS and regulates actin dynamics through Rho GTPases. Mutations in Abl and trio interacted genetically, leading to dramatic disruption of axon pathways at the CNS midline. Building upon these initial observations, we analyzed interactions between Abl, trio, and the attractive Netrin receptor frazzled (fra)/Deleted-in-Colorectal-Cancer (DCC). In fra;Abl and fra;trio double mutants, few axons crossed the midline, similar to the phenotype in trio, Abl mutants. Furthermore, mutations in Abl and trio suppressed the inappropriate midline crossover phenotype in embryos expressing the chimeric Robo-Fra receptor, consistent with an in vivo role for these molecules as Fra effectors. Fra bound Abl and Trio in coimmunoprecipitation and GST pulldown experiments, and tyrosine phosphorylation of Fra and Trio was elevated in cultured cells overexpressing Abl. Mutations in enabled (ena), another Abl substrate, suppressed the loss-of-commissure phenotype in fra, Abl, and trio mutants, as well as the Robo-Fra receptor phenotype. Together, these results suggest that Abl and Trio are effectors for multiple attractive receptors at the CNS midline, and that Ena may function during both attractive and repulsive signaling. Finally, a functional analysis of the requirement for Trio's conserved domains has been initiated. In transgenic rescue and overexpression experiments, TrioGEF1 was required for axon guidance across the CNS midline, while TrioSH3 inhibited midline crossing. Coexpression experiments with the Robo-Fra receptor and assays in other tissues and cultured cells suggest that the conserved N-terminal domain, spectrin-like repeats, and GEF2 domain may modulate GEF1 signaling in specific contexts. Future experiments must elucidate the mechanistic details of cytoskeletal control by Trio and Fra.
Author: Dominique Bagnard
Publisher: Springer Science & Business Media
ISBN: 0387767150
Category : Medical
Languages : en
Pages : 184
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This book proposes an updated view of the current knowledge of the molecular and cellular mechanisms ensuring axon growth and guidance. The introductory chapter will remind the readers of all the features of a growth cone and the mechanisms controlling its growth. From there, one enters a fabulous journey with a growth cone, a Tom Thumb story filled with molecular encounters and complex interactions leading to one of the most fantastic developmental achievements: the nervous system wiring.
Author: Hailan Hu
Publisher:
ISBN:
Category :
Languages : en
Pages : 284
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Author: Hong Iris Wan
Publisher:
ISBN:
Category :
Languages : en
Pages : 392
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Author: Jose A. Campos-Ortega
Publisher: Springer Science & Business Media
ISBN: 3662024543
Category : Science
Languages : en
Pages : 237
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" . . . but our knowledge is so weak that no philosoph er will ever be able to completely explore the nature of even a fly . . . " * Thornas Aquinas "In Syrnbolurn Apostolorum" 079 RSV p/96 This is a monograph on embryogenesis of the fruit fly Drosophi la melanogaster conceived as a reference book on morphology of embryonie development. A monograph of this extent and con tent is not yet available in the literature of Drosophila embryolo gy, and we believe that there is areal need for it. Thanks to the progress achieved during the last ten years in the fields of devel opmental and molecular genetics, work on Drosophila develop ment has considerably expanded creating an even greater need for the information that we present here. Our own interest for wildtype embryonie development arose several years ago, when we began to study the development of mutants. While those studies were going on we repeatedly had occasion to state in sufficiencies in the existing literature about the embryology of the wildtype, so that we undertook investigating many of these problems by ourselves. Convinced that several of our colleagues will have encountered similar difficulties we decided to publish the present monograph. Although not expressely recorded, Thomas Aquinas probably referred to the domestic fly and not to the fruit fly. Irrespective of which fly he meant, however, we know that Thomas was right in any case.
Author: Eric Deon Ward
Publisher:
ISBN:
Category : Axons
Languages : en
Pages : 238
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