Control of Wing Size and Proportions by Drosophila Myc

Abstract

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).

Defective Hfp-dependent transcriptional repression of dMYC is fundamental to tissue overgrowth in Drosophila XPB models

“…B-gal was detected in the cycling cells of the third instar wing pouch and reduced both along the differentiating cells at the D/V boundary and throughout the hinge domain 52,53,57 ( Fig. 2a,c), consistent with patterning of dMYC mRNA 54,62 . dMYC enhancer trap activity spanning the entire wing disc (pouch and hinge) was significantly greater in Hfp mutants compared with wild type (Fig.…”

“…The conserved domains between the Human-XPB and Drosophila-Hay protein are highlighted and include the N-terminal DNA binding domain, several helicase domains and the C-terminal domain. The Drosophila Hay nc2 allele was first identified in 1988 45,54 and characterized as a point mutation at amino-acid position 652 in the sixth helicase domain 18,40,50,51,54 . Subsequently, following ethyl methane sulfonate-induced mutagenesis, several other Hay mutants were generated in the Hay nc2 background and molecularly characterized 41,54 .…”

“…The Drosophila Hay nc2 allele was first identified in 1988 45,54 and characterized as a point mutation at amino-acid position 652 in the sixth helicase domain 18,40,50,51,54 . Subsequently, following ethyl methane sulfonate-induced mutagenesis, several other Hay mutants were generated in the Hay nc2 background and molecularly characterized 41,54 . The original Hay nc2 point mutation affects the conserved helicase domain but encodes an in-frame C-terminal domain, whereas the ethyl methane sulfonate mutants chosen for analysis here (Hay nc2rv1 , Hay nc2rv3 , Hay nc2rv7 ) contain stop codons at position 657, 380 and 441, respectively, and lack the C-terminal domain (Fig.…”

“…2a,c) 16,18,23,24,50,51,54 . dMYC mRNA is detected in the second instar hinge, which forms circular domains that surround the pouch, but is normally downregulated in third instar 44,54 , as reflected by the pattern of dMYC enhancer trap activity (Fig. 2c, white arrow).…”

Longevity and stress resistance are affected by activation of TOR/Myc in progenitor cells of Drosophila gut

“…melanogaster Myc regulates cell growth during development [13] and together with Rheb possesses oncogenic activity [14,15]. Myc may act independently to regulate ISC growth.…”