Axon repulsion from the midline of the Drosophila CNS requires slit function

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2475-2481 ◽  
Author(s):  
R. Battye ◽  
A. Stevens ◽  
J.R. Jacobs
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transgene Expression ◽  
Ectopic Expression ◽  
Growth Cones ◽  
Drosophila Embryogenesis ◽  
Putative Receptor ◽  
Midline Crossing ◽  
The Central Nervous System ◽  
Axon Repulsion

Guidance of axons towards or away from the midline of the central nervous system during Drosophila embryogenesis reflects a balance of attractive and repulsive cues originating from the midline. Here we demonstrate that Slit, a protein secreted by the midline glial cells provides a repulsive cue for the growth cones of axons and muscle cells. Embryos lacking slit function show a medial collapse of lateral axon tracts and ectopic midline crossing of ventral muscles. Transgene expression of slit in the midline restores axon patterning. Ectopic expression of slit inhibits formation of axon tracts at locations of high Slit production and misdirects axon tracts towards the midline. slit interacts genetically with roundabout, which encodes a putative receptor for growth cone repulsion.

Ectopic expression of either the Drosophila gooseberry-distal or proximal gene causes alterations of cell fate in the epidermis and central nervous system

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1151-1161 ◽  
Author(s):  
Y. Zhang ◽  
A. Ungar ◽  
C. Fresquez ◽  
R. Holmgren
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Fate ◽  
Ectopic Expression ◽  
Cell Fate Specification ◽  
Single Function ◽  
Independent Functions ◽  
Segment Polarity ◽  
The Central Nervous System ◽  
The Common

Previous studies have shown that the segment polarity locus gooseberry, which contains two closely related transcripts gooseberry-proximal and gooseberry-distal, is required for proper development in both the epidermis and the central nervous system of Drosophila. In this study, the roles of the gooseberry proteins in the process of cell fate specification have been examined by generating two fly lines in which either gooseberry-distal or gooseberry-proximal expression is under the control of an hsp70 promoter. We have found that ectopic expression of either gooseberry protein causes cell fate transformations that are reciprocal to those of a gooseberry deletion mutant. Our results suggest that the gooseberry-distal protein is required for the specification of naked cuticle in the epidermis and specific neuroblasts in the central nervous system. These roles may reflect independent functions in neuroblasts and epidermal cells or a single function in the common ectodermal precursor cells. The gooseberry-proximal protein is also found in the same neuroblasts as gooseberry-distal and in the descendants of these cells.

scholarly journals Drosophila Zic family member odd-paired is needed for adult post-ecdysis maturation

Open Biology ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 190245
Author(s):  
Eléanor Simon ◽  
Sergio Fernández de la Puebla ◽  
Isabel Guerrero
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Family Member ◽  
Ectopic Expression ◽  
Functional Conservation ◽  
The Central Nervous System ◽  
Behavioural Sequence

Specific neuropeptides regulate in arthropods the shedding of the old cuticle (ecdysis) followed by maturation of the new cuticle. In Drosophila melanogaster , the last ecdysis occurs at eclosion from the pupal case, with a post-eclosion behavioural sequence that leads to wing extension, cuticle stretching and tanning. These events are highly stereotyped and are controlled by a subset of crustacean cardioactive peptide (CCAP) neurons through the expression of the neuropeptide Bursicon (Burs). We have studied the role of the transcription factor Odd-paired (Opa) during the post-eclosion period. We report that opa is expressed in the CCAP neurons of the central nervous system during various steps of the ecdysis process and in peripheral CCAP neurons innerving the larval muscles involved in adult ecdysis. We show that its downregulation alters Burs expression in the CCAP neurons. Ectopic expression of Opa, or the vertebrate homologue Zic2 , in the CCAP neurons also affects Burs expression, indicating an evolutionary functional conservation. Finally, our results show that, independently of its role in Burs regulation, Opa prevents death of CCAP neurons during larval development.

scholarly journals A novel Dbl family RhoGEF promotes Rho-dependent axon attraction to the central nervous system midline in Drosophila and overcomes Robo repulsion

2001 ◽  
Vol 155 (7) ◽  
pp. 1117-1122 ◽  
Author(s):  
Greg J. Bashaw ◽  
Hailan Hu ◽  
Catherine D. Nobes ◽  
Corey S. Goodman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rho Gtpases ◽  
Ectopic Expression ◽  
Nucleotide Exchange ◽  
Loss Of Function ◽  
Guanine Nucleotide Exchange ◽  
Positive Regulators ◽  
The Central Nervous System ◽  
Rho Gef

The key role of the Rho family GTPases Rac, Rho, and CDC42 in regulating the actin cytoskeleton is well established (Hall, A. 1998. Science. 279:509–514). Increasing evidence suggests that the Rho GTPases and their upstream positive regulators, guanine nucleotide exchange factors (GEFs), also play important roles in the control of growth cone guidance in the developing nervous system (Luo, L. 2000. Nat. Rev. Neurosci. 1:173–180; Dickson, B.J. 2001. Curr. Opin. Neurobiol. 11:103–110). Here, we present the identification and molecular characterization of a novel Dbl family Rho GEF, GEF64C, that promotes axon attraction to the central nervous system midline in the embryonic Drosophila nervous system. In sensitized genetic backgrounds, loss of GEF64C function causes a phenotype where too few axons cross the midline. In contrast, ectopic expression of GEF64C throughout the nervous system results in a phenotype in which far too many axons cross the midline, a phenotype reminiscent of loss of function mutations in the Roundabout (Robo) repulsive guidance receptor. Genetic analysis indicates that GEF64C expression can in fact overcome Robo repulsion. Surprisingly, evidence from genetic, biochemical, and cell culture experiments suggests that the promotion of axon attraction by GEF64C is dependent on the activation of Rho, but not Rac or Cdc42.

scholarly journals Gene Regulation Systems for Gene Therapy Applications in the Central Nervous System

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jerusha Naidoo ◽  
Deborah Young
Keyword(s):  
Gene Therapy ◽  
Central Nervous System ◽  
Nervous System ◽  
Gene Regulation ◽  
Transgene Expression ◽  
Endogenous Gene ◽  
Temporal Regulation ◽  
Regulatory Systems ◽  
Substantial Progress ◽  
The Central Nervous System

Substantial progress has been made in the development of novel gene therapy strategies for central nervous system (CNS) disorders in recent years. However, unregulated transgene expression is a significant issue limiting human applications due to the potential side effects from excessive levels of transgenic protein that indiscriminately affect both diseased and nondiseased cells. Gene regulation systems are a tool by which tight tissue-specific and temporal regulation of transgene expression may be achieved. This review covers the features of ideal regulatory systems and summarises the mechanics of current exogenous and endogenous gene regulation systems and their utility in the CNS.

scholarly journals Commissureless is required both in commissural neurones and midline cells for axon guidance across the midline

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2947-2956 ◽  
Author(s):  
Marios Georgiou ◽  
Guy Tear
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rna Interference ◽  
Protein Expression ◽  
Axon Guidance ◽  
Contralateral Side ◽  
Commissural Axons ◽  
Midline Crossing ◽  
The Central Nervous System ◽  
Midline Cells

In the absence of Commissureless (Comm) function, axons are unable to extend across the central nervous system midline. Comm downregulates levels of Roundabout (Robo), a receptor for the midline repellent Slit, in order to allow axons to cross the midline. comm transcript is expressed at high levels in the midline glia and Comm protein accumulates on axons at the midline. This has led to the hypothesis that Comm moves from the midline glia to the axons, where it can reduce Robo levels. We have found that expression of Comm in the midline cells is unable to rescue the comm phenotype and that tagged versions of Comm are not transferred to axons. A re-examination of Comm protein expression and the use of targeted RNA interference reveal that correct midline crossing requires that Comm is expressed in the commissural axons and midline glia. We suggest that accumulation of Comm protein at the midline spatially limits Comm activity and prevents it from being active on the contralateral side of the central nervous system.

scholarly journals Long-term Transgene Expression in the Central Nervous System Using DNA Nanoparticles

2009 ◽  
Vol 17 (4) ◽  
pp. 641-650 ◽  
Author(s):  
David M Yurek ◽  
Anita M Fletcher ◽  
George M Smith ◽  
Kim B Seroogy ◽  
Assem G Ziady ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transgene Expression ◽  
Dna Nanoparticles ◽  
The Central Nervous System
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