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Studies on the role of Dally-like during Drosophila development

Khare, Narmada LU (2002)
Abstract
A cell is constantly subjected to cues from its surroundings in the form of signalling molecules e.g. Wingless (Wg), Insulin-like growth factor (IGF). As a result, important decisions regarding processes like growth, division, differentiation or migration are made. The work presented here attempts to characterise a cell-surface molecule in Drosophila that helps in the reception of some of these signals by acting as a low-affinity co-receptor. Cloning and sequencing of a fragment from the Drosophila cDNA library revealed it to be a glypican, a heparan sulfate proteoglycan (HSPG) attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. The segmentally repeated expression pattern of dly in embryos and the phenotypes caused... (More)
A cell is constantly subjected to cues from its surroundings in the form of signalling molecules e.g. Wingless (Wg), Insulin-like growth factor (IGF). As a result, important decisions regarding processes like growth, division, differentiation or migration are made. The work presented here attempts to characterise a cell-surface molecule in Drosophila that helps in the reception of some of these signals by acting as a low-affinity co-receptor. Cloning and sequencing of a fragment from the Drosophila cDNA library revealed it to be a glypican, a heparan sulfate proteoglycan (HSPG) attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. The segmentally repeated expression pattern of dly in embryos and the phenotypes caused by the dsRNAi experiments suggested that it may have a role in Wg signalling. Ectopic expression of dly showed that it may function by accumulating Wg molecules near Frizzled/Dfrizzled2, the high affinity receptors. dly mutants have small body size, eyes and wings, but larger ommatidia and wing hairs as compared to the wild type flies. The large, disorganised ommatidia are reminiscent of those in mutant dpten, a negative regulator or IGF signalling. Our studies showed that dly and dpten are genetic enhancers of each other, suggesting that Dly too may be a suppressor of IGF signalling. However, the interactions seem to be more complicated in the central nervous system (CNS), where Dly and IGF are expressed. Mutations in both genes showed loss of CNS organisation. Surprisingly, the double mutants showed an enhancement of these defects. This led us to propose that Dly may modulate signalling by the same molecule in a tissue-specific manner. (Less)
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author
supervisor
opponent
  • Dr. DeLotto, Robert
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Clinical biology, Drosophila, Dally-like, proteoglycans, signal transduction, Klinisk biologi
pages
110 pages
publisher
Developmental biology
defense location
GK-Salen, BMC, Lund
defense date
2002-03-28 10:00:00
ISBN
91-628-5175-6
language
English
LU publication?
yes
additional info
Article: 1. Dally-like protein, a new Drosophila glypican with expression overlapping with wingless.Khare N. and Baumgartner S. (2000). Mech Dev. 99(1-2):199-202. Article: 2. Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless.Baeg G. H., Lin X., Khare N., Baumgartner S., Perrimon N. (2001). Development. 128(1):87-94. Article: 3. Dally-like, a Drosophila glypican, regulates cell size via modulation of IGF signalling.Waldrip W. R., Reuter J., Khare N., Sekelsky J., Baumgartner S., Selleck S. B. (2002). (Submitted). Article: 4. Dally-like and Drosophila CNS: A role of glypicans in the developing nervous system.Khare N., Waldrip W. R., Baumgartner S., Selleck S. B. (Manuscript). Article: 5. Expression patterns of two new members of the Semaphorin family in Drosophila suggest early functions during embryogenesis.Khare N., Fascetti N., DaRocha S., Chiquet-Ehrismann R., Baumgartner S. (2000). Mech Dev. 91(1-2):393-7. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Developmental biology (LUR000007)
id
003a9d3f-c28e-408d-95b4-026b1b11c067 (old id 464435)
date added to LUP
2016-04-04 11:13:02
date last changed
2020-04-15 14:06:42
@phdthesis{003a9d3f-c28e-408d-95b4-026b1b11c067,
  abstract     = {A cell is constantly subjected to cues from its surroundings in the form of signalling molecules e.g. Wingless (Wg), Insulin-like growth factor (IGF). As a result, important decisions regarding processes like growth, division, differentiation or migration are made. The work presented here attempts to characterise a cell-surface molecule in Drosophila that helps in the reception of some of these signals by acting as a low-affinity co-receptor. Cloning and sequencing of a fragment from the Drosophila cDNA library revealed it to be a glypican, a heparan sulfate proteoglycan (HSPG) attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. The segmentally repeated expression pattern of dly in embryos and the phenotypes caused by the dsRNAi experiments suggested that it may have a role in Wg signalling. Ectopic expression of dly showed that it may function by accumulating Wg molecules near Frizzled/Dfrizzled2, the high affinity receptors. dly mutants have small body size, eyes and wings, but larger ommatidia and wing hairs as compared to the wild type flies. The large, disorganised ommatidia are reminiscent of those in mutant dpten, a negative regulator or IGF signalling. Our studies showed that dly and dpten are genetic enhancers of each other, suggesting that Dly too may be a suppressor of IGF signalling. However, the interactions seem to be more complicated in the central nervous system (CNS), where Dly and IGF are expressed. Mutations in both genes showed loss of CNS organisation. Surprisingly, the double mutants showed an enhancement of these defects. This led us to propose that Dly may modulate signalling by the same molecule in a tissue-specific manner.},
  author       = {Khare, Narmada},
  isbn         = {91-628-5175-6},
  language     = {eng},
  publisher    = {Developmental biology},
  school       = {Lund University},
  title        = {Studies on the role of Dally-like during Drosophila development},
  year         = {2002},
}