Action of<i>fat, four-jointed, dachsous</i>and<i>dachs</i>in distal-to-proximal wing signaling

Cho, Eunjoo; Irvine, Kenneth D.

doi:10.1242/dev.01315

Cited by 150 publications

(193 citation statements)

References 42 publications

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“…Previously, we described a pathway in which signaling downstream of Fat is mediated by its antagonism of the unconventional myosin Dachs (7,14,21). We also identified another Drosophila tumor suppressor, discs overgrown (dco) (22), as a kinase that acts genetically upstream of dachs within the Fat pathway (7).…”

Section: Results Fat or Ex Mutants Can Be Partially Rescued By Wts Ovmentioning

confidence: 99%

Fat and Expanded act in parallel to regulate growth through Warts

Feng

Irvine

2007

Proc. Natl. Acad. Sci. U.S.A.

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117

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The conserved Drosophila tumor suppressors Fat and Expanded have both recently been implicated in regulating the activity of the Warts tumor suppressor. However, there has been disagreement as to the nature of the links among Fat, Expanded, and Warts and the significance of these links to growth control. We report here that mutations in either expanded or fat can be rescued to viability simply by overexpressing Warts, indicating that their essential function is their influence on Warts rather than reported effects on endocytosis or other pathways. These rescue experiments also separate the transcriptional from the planar cell polarity branches of Fat signaling and reveal that Expanded does not directly affect polarity. We also investigate the relationship between expanded and fat and show, contrary to prior reports, that they have additive effects on imaginal disk growth and development. Although mutation of fat can cause partial loss of Expanded protein from the membrane, mutation of fat promotes growth even when Expanded is overexpressed and accumulates at its normal subapical location. These observations argue against recent proposals that Fat acts simply as a receptor for the Hippo signaling pathway and instead support the proposal that Fat and Expanded can act in parallel to regulate Warts through distinct mechanisms.Drosophila ͉ Hippo ͉ protocadherin

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Section: Results Fat or Ex Mutants Can Be Partially Rescued By Wts Ovmentioning

confidence: 99%

Fat and Expanded act in parallel to regulate growth through Warts

Feng

Irvine

2007

Proc. Natl. Acad. Sci. U.S.A.

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117

130

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“…Region-specific cues may be provided by the hinge selector Hth and the wing selector Vg and by Fat/Hippo signaling. The cadherins Fat and Dachsous regulate proximal (hinge) wing growth via Hippo signaling, whereas a feed-forward auto-regulatory loop Vg brings about expansion of distal wing (blade) fates (Cho and Irvine 2004;Cho et al 2006;Zecca and Struhl 2007b;Rogulja et al 2008). Regulation in both cases appears to be in response to signaling from Wg and Dpp.…”

Section: Discussionmentioning

confidence: 99%

Control of Wing Size and Proportions by Drosophila Myc

Wu¹,

Johnston

2010

Genetics

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Generation of an organ of appropriate size and shape requires mechanisms that coordinate growth and patterning, but how this is achieved is not understood. Here we examine the role of the growth regulator dMyc in this process during Drosophila wing imaginal disc development. We find that dMyc is expressed in a dynamic pattern that correlates with fate specification of different regions of the wing disc, leading us to hypothesize that dMyc expression in each region directs its growth. Consistent with this view, clonal analysis of growth in each region demonstrated distinct temporal requirements for dMyc that match its expression. Surprisingly, however, experiments in which dMyc expression is manipulated reveal that the endogenous pattern has only a minor influence on wing shape. Indeed, when dMyc function is completely lacking in the wing disc over most of its development, the discs grow slowly and are small in size but appear morphologically normal. Our experiments indicate, therefore, that rather than directly influence differential growth in the wing disc, the pattern of dMyc expression augments growth directed by other regulators. Overall, however, an appropriate level of dMyc expression in the wing disc is necessary for each region to achieve a proportionately correct size.H OW pattern and growth are coordinated during development to produce an organ of correct size and shape is a central question in biology. The Drosophila wing is an elegant, self-organizing system that is ideal for the study of this coordination. Wing growth is coupled to the specification of cell fates, and these processes are regulated by a small number of conserved signaling pathways and selector proteins. The wing develops from the wing imaginal disc, a proliferating epithelium housed in the larva that also gives rise to the dorsal thorax of the adult fly. The adult wing includes the blade, made from wing pouch (WP) cells of the wing disc, and hinge structures, which are formed by cells immediately proximal to the WP.Wing development proceeds through a series of steps in which regions of fates are specified. Discs begin development composed of cells with either anterior (A) or posterior (P) identity and subsequently undergo several subdivisions. Early in the second larval instar (L2), the action of Wingless (Wg) and the EGF receptor divide the wing disc into large domains that define the body wall and wing (Wang et al. 2000;Zecca and Struhl 2002).

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“…Imaginal discs were fixed and stained as described in ref. 23, using mouse anti-Wg [1:800, 4D4, Developmental Studies Hybridoma Bank (DSHB)], rat anti-DE-Cadherin (1:40, DCAD2, DSHB), rabbit anti-Gal4 (1:400, preabsorbed, Santa Cruz Biotechnology), mouse anti-Myc (9E10, 1:800, Babco), mouse anti-V5 (1:400 preabsorbed, Invitrogen) and rat anti-Fat (1:1,600). Fluorescent stains were captured on a Leica TCS SP5 confocal microscope.…”

Section: Methodsmentioning

confidence: 99%

Processing and phosphorylation of the Fat receptor

Feng

Irvine

2009

Proc. Natl. Acad. Sci. U.S.A.

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140

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The Drosophila tumor suppressors fat and discs overgrown (dco) function within an intercellular signaling pathway that controls growth and polarity. fat encodes a transmembrane receptor, but post-translational regulation of Fat has not been described. We show here that Fat is subject to a constitutive proteolytic processing, such that most or all cell surface Fat comprises a heterodimer of stably associated N-and C-terminal fragments. The cytoplasmic domain of Fat is phosphorylated, and this phosphorylation is promoted by the Fat ligand Dachsous. dco encodes a kinase that influences Fat signaling, and Dco is able to promote the phosphorylation of the Fat intracellular domain in cultured cells and in vivo.

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Action offat, four-jointed, dachsousanddachsin distal-to-proximal wing signaling

Cited by 150 publications

References 42 publications

Fat and Expanded act in parallel to regulate growth through Warts

Fat and Expanded act in parallel to regulate growth through Warts

Control of Wing Size and Proportions by Drosophila Myc

Processing and phosphorylation of the Fat receptor

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