Genomes and Genes
Gene Symbol: Dad
Description: Daughters against dpp
Alias: 1883, CG5201, DAD, Dad1, Dmel\CG5201, EP(3)3196, EP3196, anon-EST:fe1F5, dad, l(3)j1E4, daughters against dpp, CG5201-PA, CG5201-PB, CG5201-PC, Dad-PA, Dad-PB, Dad-PC, anon-fast-evolving-1F5, daughter against dpp, daughters against Dpp
Species: fruit fly
- Weiss A, Charbonnier E, Ellertsdottir E, Tsirigos A, Wolf C, Schuh R, et al. A conserved activation element in BMP signaling during Drosophila development. Nat Struct Mol Biol. 2010;17:69-76 pubmed publisher..We have now isolated the minimal enhancer of the dad gene and discovered a short motif we termed the activating element (AE)...
- Muller B, Hartmann B, Pyrowolakis G, Affolter M, Basler K. Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient. Cell. 2003;113:221-33 pubmed..Together, our results provide the molecular framework for a mechanism by which the extracellular Dpp/BMP morphogen establishes a finely tuned, graded read-out of transcriptional repression. ..
- Bradley P, Myat M, Comeaux C, Andrew D. Posterior migration of the salivary gland requires an intact visceral mesoderm and integrin function. Dev Biol. 2003;257:249-62 pubmed..These findings suggest that salivary tube dimensions may be an intrinsic property of salivary gland cells. ..
- Adachi Yamada T, O Connor M. Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. Dev Biol. 2002;251:74-90 pubmed..This phenomenon is likely related to the process of cell competition, and we suggest that it is an evolutionarily important mechanism that helps prevent abnormal tissue specification and growth during development. ..
- Martín F, Pérez Garijo A, Moreno E, Morata G. The brinker gradient controls wing growth in Drosophila. Development. 2004;131:4921-30 pubmed..Brk appears to downregulate the activity of genes that control cell proliferation, such as bantam. ..
- Liang Y, Lin X, Liang M, Brunicardi F, Ten Dijke P, Chen Z, et al. dSmurf selectively degrades decapentaplegic-activated MAD, and its overexpression disrupts imaginal disc development. J Biol Chem. 2003;278:26307-10 pubmed..dSmurf selectively interacted with MAD, but not Medea and Dad, and the MAD-dSmurf interaction was induced by constitutively active DPP type I receptor thickveins...
- Xi R, Doan C, Liu D, Xie T. Pelota controls self-renewal of germline stem cells by repressing a Bam-independent differentiation pathway. Development. 2005;132:5365-74 pubmed..In pelo mutant GSCs, Bmp signaling activity detected by Dad-lacZ expression is downregulated, but bam expression is still repressed...
- Martín Castellanos C, Edgar B. A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing. Development. 2002;129:1003-13 pubmed..Conversely, autonomously inhibiting Dpp signaling using a pathway specific inhibitor, Dad, or a mutation in tkv, slowed wing cell growth and division, also in a coordinate fashion...
- Li Z, Zhang Y, Han L, Shi L, Lin X. Trachea-derived dpp controls adult midgut homeostasis in Drosophila. Dev Cell. 2013;24:133-43 pubmed publisher..This work will provide important insights into the mechanisms of tissue homeostasis control by interorgan communication...
- McCabe B, Hom S, Aberle H, Fetter R, Marques G, Haerry T, et al. Highwire regulates presynaptic BMP signaling essential for synaptic growth. Neuron. 2004;41:891-905 pubmed..These results reveal a balance between positive BMP signaling and negative regulation by Highwire, governing the growth of neuromuscular synapses. ..
- Kirilly D, Wang S, Xie T. Self-maintained escort cells form a germline stem cell differentiation niche. Development. 2011;138:5087-97 pubmed publisher..Here, we propose that ECs form a niche that controls GSC lineage differentiation and is maintained by a non-stem cell mechanism. ..
- Zhao R, Xuan Y, Li X, Xi R. Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila. Aging Cell. 2008;7:344-54 pubmed publisher..We suggest that niche functional decay may be an important mechanism for stem cell aging and system failure. ..
- Casanueva M, Ferguson E. Germline stem cell number in the Drosophila ovary is regulated by redundant mechanisms that control Dpp signaling. Development. 2004;131:1881-90 pubmed..In contrast to the above model, we find that an enhancer trap inserted near the Dpp target gene, Daughters against Dpp (Dad), is expressed in additional somatic cells within the germarium, suggesting that Dpp protein may be ..
- Vuilleumier R, Springhorn A, Patterson L, Koidl S, Hammerschmidt M, Affolter M, et al. Control of Dpp morphogen signalling by a secreted feedback regulator. Nat Cell Biol. 2010;12:611-7 pubmed publisher..We show that Pent interacts with the glypican Dally to control Dpp distribution and provide evidence that proper establishment of the BMP morphogen gradient requires the inbuilt feedback loop embodied by Pent. ..
- Gibson M, Lehman D, Schubiger G. Lumenal transmission of decapentaplegic in Drosophila imaginal discs. Dev Cell. 2002;3:451-60 pubmed..These results are consistent with lumenal transmission of the DPP survival signal during imaginal disc development. ..
- Rogulja D, Irvine K. Regulation of cell proliferation by a morphogen gradient. Cell. 2005;123:449-61 pubmed..Conversely, uniform activation of the DPP pathway inhibits cell proliferation in medial wing cells. Our observations provide a direct demonstration that the slope of a morphogen gradient regulates growth during development. ..
- Kai T, Spradling A. An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells. Proc Natl Acad Sci U S A. 2003;100:4633-8 pubmed..Thus, empty niches can persist, signal incoming cells, and support ectopic proliferation. Similar events may underlie some disease states. ..
- Guo Z, Wang Z. The glypican Dally is required in the niche for the maintenance of germline stem cells and short-range BMP signaling in the Drosophila ovary. Development. 2009;136:3627-35 pubmed publisher..We propose that Dally ensures high-level BMP signaling in the ovarian niche and thus female GSC determination. ..
- Ward E, Shcherbata H, Reynolds S, Fischer K, Hatfield S, Ruohola Baker H. Stem cells signal to the niche through the Notch pathway in the Drosophila ovary. Curr Biol. 2006;16:2352-8 pubmed..Demonstration that stem cells can contribute to niche function has far-reaching consequences for stem cell therapies and may provide insight into how cancer can spread throughout an organism via populations of cancer stem cells. ..
- Wartlick O, Mumcu P, Kicheva A, Bittig T, Seum C, Jülicher F, et al. Dynamics of Dpp signaling and proliferation control. Science. 2011;331:1154-9 pubmed publisher..Our observations are consistent with a growth control mechanism based on temporal changes of cellular morphogen signaling levels. For a scaling gradient, this mechanism generates position-independent growth rates. ..
- Xia L, Jia S, Huang S, Wang H, Zhu Y, Mu Y, et al. The Fused/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response. Cell. 2010;143:978-90 pubmed publisher..We observed similar roles for Fu during embryonic development in zebrafish and in human cell culture, implying broad conservation of this mechanism. ..
- Marty T, Muller B, Basler K, Affolter M. Schnurri mediates Dpp-dependent repression of brinker transcription. Nat Cell Biol. 2000;2:745-9 pubmed..The existence of several Shn-like proteins in vertebrates and the observation that Brk functions in BMP signalling in Xenopus indicates that a similar regulatory cascade may be conserved in higher organisms. ..
- Leatherman J, Dinardo S. Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes. Nat Cell Biol. 2010;12:806-11 pubmed publisher..This work also reconciles key differences in GSC renewal between Drosophila testis and ovary niches, and highlights how a niche can coordinate the production of distinct lineages by having one stem cell type rely on a second. ..
- Horsfield J, Penton A, Secombe J, Hoffman F, Richardson H. decapentaplegic is required for arrest in G1 phase during Drosophila eye development. Development. 1998;125:5069-78 pubmed..In addition, our results provide evidence for a Dpp-independent mechanism that acts in the posterior part of the morphogenetic furrow to maintain G1 arrest. ..
- Xie T, Spradling A. decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell. 1998;94:251-60 pubmed..We constructed mutant germline stem cell clones to show that the dpp signal is directly received by germline stem cells. Thus, dpp signaling helps define a niche that controls germline stem cell proliferation. ..
- Ables E, Drummond Barbosa D. The steroid hormone ecdysone functions with intrinsic chromatin remodeling factors to control female germline stem cells in Drosophila. Cell Stem Cell. 2010;7:581-92 pubmed publisher..Our findings support a link between systemic steroid hormones and the intrinsic chromatin remodeling machinery as a potential mechanism to promote broad transcriptional programs required for adult stem cell self-renewal. ..
- Widmann T, Dahmann C. Dpp signaling promotes the cuboidal-to-columnar shape transition of Drosophila wing disc epithelia by regulating Rho1. J Cell Sci. 2009;122:1362-73 pubmed publisher..Our results identify a cell-autonomous role for Dpp signaling in promoting and maintaining the elongated columnar shape of wing disc cells and suggest that Dpp signaling acts by regulating Rho1 and MRLC. ..
- Lindner J, Hillman P, Barrett A, Jackson M, Perry T, Park Y, et al. The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts. BMC Dev Biol. 2007;7:121 pubmed..These studies also highlight the fact that Trol function is not dedicated to a single molecular mechanism, but is capable of regulating different growth factor pathways depending on the cell-type and event underway. ..
- Goold C, Davis G. The BMP ligand Gbb gates the expression of synaptic homeostasis independent of synaptic growth control. Neuron. 2007;56:109-23 pubmed
- Shi W, Chen Y, Gan G, Wang D, Ren J, Wang Q, et al. Brain tumor regulates neuromuscular synapse growth and endocytosis in Drosophila by suppressing mad expression. J Neurosci. 2013;33:12352-63 pubmed publisher..These results together reveal an important and previously unidentified role for Brat in synaptic development and endocytosis mediated by suppression of BMP signaling. ..
- Song X, Call G, Kirilly D, Xie T. Notch signaling controls germline stem cell niche formation in the Drosophila ovary. Development. 2007;134:1071-80 pubmed..Our results indicate that Notch signaling is important for formation and maintenance of the GSC niche, and that cap cells help determine niche size and function. ..
- Tsuneizumi K, Nakayama T, Kamoshida Y, Kornberg T, Christian J, Tabata T. Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature. 1997;389:627-31 pubmed..We have now isolated a gene, Daughters against dpp (Dad), whose transcription is induced by Dpp...
- König A, Yatsenko A, WEISS M, Shcherbata H. Ecdysteroids affect Drosophila ovarian stem cell niche formation and early germline differentiation. EMBO J. 2011;30:1549-62 pubmed publisher..Additionally, when ecdysone signalling is perturbed during the process of somatic stem cell niche establishment enlarged functional niches able to host additional stem cells are formed. ..
- Sweeney S, Davis G. Unrestricted synaptic growth in spinster-a late endosomal protein implicated in TGF-beta-mediated synaptic growth regulation. Neuron. 2002;36:403-16 pubmed..Furthermore, mutations in Dad, an inhibitory Smad, cause synapse overgrowth...
- Wang L, Li Z, Cai Y. The JAK/STAT pathway positively regulates DPP signaling in the Drosophila germline stem cell niche. J Cell Biol. 2008;180:721-8 pubmed publisher..JAK/STAT signaling may also regulate dpp expression in the male GSC niche, suggesting a common origin of female and male GSC niches. ..
- O Connor Giles K, Ho L, Ganetzky B. Nervous wreck interacts with thickveins and the endocytic machinery to attenuate retrograde BMP signaling during synaptic growth. Neuron. 2008;58:507-18 pubmed publisher..We propose that Nwk functions at the interface of endocytosis and BMP signaling to ensure proper synaptic growth by negatively regulating Tkv to set limits on this positive growth signal. ..
- Song X, Wong M, Kawase E, Xi R, Ding B, McCarthy J, et al. Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Development. 2004;131:1353-64 pubmed..Thus, niche signals directly repress differentiation-promoting genes in stem cells in order to maintain stem cell self-renewal. ..
- Shivdasani A, Ingham P. Regulation of stem cell maintenance and transit amplifying cell proliferation by tgf-beta signaling in Drosophila spermatogenesis. Curr Biol. 2003;13:2065-72 pubmed
- Rodal A, Blunk A, Akbergenova Y, Jorquera R, Buhl L, Littleton J. A presynaptic endosomal trafficking pathway controls synaptic growth signaling. J Cell Biol. 2011;193:201-17 pubmed publisher..Our results define a presynaptic trafficking pathway mediated by SNX16, NWK, and the ESCRT complex that functions to control synaptic growth signaling at the interface between endosomal compartments. ..
- Raftery L, Sutherland D. TGF-beta family signal transduction in Drosophila development: from Mad to Smads. Dev Biol. 1999;210:251-68 pubmed..Identification of more ligand sequences and demonstration of a functional Drosophila activin-like signal transduction pathway suggest that all TGF-beta signal transduction pathways are present in flies. ..
- Eliazer S, Shalaby N, Buszczak M. Loss of lysine-specific demethylase 1 nonautonomously causes stem cell tumors in the Drosophila ovary. Proc Natl Acad Sci U S A. 2011;108:7064-9 pubmed publisher..The role of Lsd1 in regulating niche-specific signals may have important implications for understanding how disruption of its mammalian homolog contributes to cancer and metastasis. ..
- Foronda D, Pérez Garijo A, Martín F. Dpp of posterior origin patterns the proximal region of the wing. Mech Dev. 2009;126:99-106 pubmed publisher..Since there is a similar expression in the haltere disc, we suggest that this late appearing posterior Dpp activity may be an attribute of dorsal thoracic discs. ..
- Kawase E, Wong M, Ding B, Xie T. Gbb/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis. Development. 2004;131:1365-75 pubmed..dpp signaling is known to be essential for maintaining GSCs in the Drosophila ovary. This study further suggests that both Drosophila male and female GSCs use Bmp signals to maintain GSCs. ..
- Tanaka R, Takase Y, Kanachi M, Enomoto Katayama R, Shirai T, Nakagoshi H. Notch-, Wingless-, and Dpp-mediated signaling pathways are required for functional specification of Drosophila midgut cells. Dev Biol. 2007;304:53-61 pubmed..These results provide valuable insights into the molecular mechanism underlying functional specification. ..
- Massague J, Wotton D. Transcriptional control by the TGF-beta/Smad signaling system. EMBO J. 2000;19:1745-54 pubmed
- Acharya P, Negre N, Johnston J, Wei Y, White K, Henry R, et al. Evidence for autoregulation and cell signaling pathway regulation from genome-wide binding of the Drosophila retinoblastoma protein. G3 (Bethesda). 2012;2:1459-72 pubmed publisher..Many of these targeted genes are bound by Rbf1 homologs in human cells, indicating that a conserved role of RB proteins may be to adjust the set point of interlinked signaling networks essential for growth and development. ..
- Barrio R, López Varea A, Casado M, de Celis J. Characterization of dSnoN and its relationship to Decapentaplegic signaling in Drosophila. Dev Biol. 2007;306:66-81 pubmed
- Crickmore M, Mann R. Hox control of morphogen mobility and organ development through regulation of glypican expression. Development. 2007;134:327-34 pubmed..Our results suggest that Dpp mobility is biased towards cells with higher levels of Dally and that selector genes modulate organ development by regulating glypican levels. ..
- Inoue H, Imamura T, Ishidou Y, Takase M, Udagawa Y, Oka Y, et al. Interplay of signal mediators of decapentaplegic (Dpp): molecular characterization of mothers against dpp, Medea, and daughters against dpp. Mol Biol Cell. 1998;9:2145-56 pubmed..Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling...
- Beich Frandsen M, AragÃ³n E, Llimargas M, Benach J, Riera A, Pous J, et al. Structure of the N-terminal domain of the protein Expansion: an 'Expansion' to the Smad MH2 fold. Acta Crystallogr D Biol Crystallogr. 2015;71:844-53 pubmed publisher..Based on the structural similarities to the MH2 fold, it is proposed that the NÎ±-MH2 domain should be classified as a new member of the Smad/FHA superfamily. ..
- Zahedi B, Shen W, Xu X, Chen X, Mahey M, Harden N. Leading edge-secreted Dpp cooperates with ACK-dependent signaling from the amnioserosa to regulate myosin levels during dorsal closure. Dev Dyn. 2008;237:2936-46 pubmed publisher..ACK function in the amnioserosa may generate a signal cooperating with Dpp secreted from the epidermis in driving zip expression in these two tissues, ensuring that cell shape changes in dorsal closure occur in a coordinated manner. ..
- O Keefe D, Prober D, Moyle P, Rickoll W, Edgar B. Egfr/Ras signaling regulates DE-cadherin/Shotgun localization to control vein morphogenesis in the Drosophila wing. Dev Biol. 2007;311:25-39 pubmed..Ras, therefore, regulates both the transcriptional responses necessary for vein cell identity, and the cell adhesive changes that determine vein and intervein cell morphology. ..
- de Navascués J, Modolell J. tailup, a LIM-HD gene, and Iro-C cooperate in Drosophila dorsal mesothorax specification. Development. 2007;134:1779-88 pubmed..Our data support a model in which the EGFR and Dpp signalling pathways, with their respective downstream Iro-C and tup genes, converge and cooperate to commit cells to the notum developmental fate. ..
- Ribeiro C, Neumann M, Affolter M. Genetic control of cell intercalation during tracheal morphogenesis in Drosophila. Curr Biol. 2004;14:2197-207 pubmed..Only the combined action of these signaling systems allows efficient branch elongation and the formation of morphologically distinct branches. ..
- Umemori M, Takemura M, Maeda K, Ohba K, Adachi Yamada T. Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal. Dev Biol. 2007;308:68-81 pubmed..These are the mechanisms for generating secondary phenotypes when a single signaling factor Omb fails to function. ..
- Gilboa L, Lehmann R. Repression of primordial germ cell differentiation parallels germ line stem cell maintenance. Curr Biol. 2004;14:981-6 pubmed..The similarity in the genes necessary for GSC maintenance and the repression of PGC differentiation suggest that PGCs and GSCs may be functionally equivalent and that the larval gonad functions as a "PGC niche". ..