Recruitment of cells into the Drosophila wing primordium by a feed-forward circuit of vestigial autoregulation

The Drosophila wing primordium is defined by expression of the selector gene vestigial (vg) in a discrete subpopulation of cells within the wing imaginal disc. Following the early segregation of the disc into dorsal (D) and ventral (V) compartments, vg expression is governed by signals generated along the boundary between the two compartments. Short-range DSL (Delta/Serrate/LAG-2)-Notch signaling between D and V cells drives vg expression in `border' cells that flank the boundary. It also induces these same cells to secrete the long-range morphogen Wingless (Wg), which drives vg expression in surrounding cells up to 25-30 cell diameters away. Here, we show that Wg signaling is not sufficient to activate vg expression away from the D-V boundary. Instead, Wg must act in combination with a short-range signal produced by cells that already express vg. We present evidence that this vg-dependent, vg-inducing signal feeds forward from one cell to the next to entrain surrounding cells to join the growing wing primordium in response to Wg. We propose that Wg promotes the expansion of the wing primordium following the D-V segregation by fueling this non-autonomous autoregulatory mechanism.

[1]  W. Gelbart,et al.  Wing formation in Drosophila melanogaster requires decapentaplegic gene function along the anterior-posterior compartment boundary , 1990, Mechanisms of Development.

[2]  T. Klein,et al.  Different spatial and temporal interactions between Notch, wingless, and vestigial specify proximal and distal pattern elements of the wing in Drosophila. , 1998, Developmental biology.

[3]  S. Carroll,et al.  Control of a Genetic Regulatory Network by a Selector Gene , 2001, Science.

[4]  T. Klein,et al.  The vestigial gene product provides a molecular context for the interpretation of signals during the development of the wing in Drosophila. , 1999, Development.

[5]  S. Cohen,et al.  Specification of the wing by localized expression of wingless protein , 1996, Nature.

[6]  S. Carroll,et al.  Organization of wing formation and induction of a wing-patterning gene at the dorsal/ventral compartment boundary , 1994, Nature.

[7]  S. Carroll,et al.  Pattern formation in a secondary field: a hierarchy of regulatory genes subdivides the developing Drosophila wing disc into discrete subregions. , 1993, Development.

[8]  G. Struhl,et al.  Direct and Long-Range Action of a Wingless Morphogen Gradient , 1996, Cell.

[9]  S. Blair,et al.  Notch regulates wingless expression and is not required for reception of the paracrine wingless signal during wing margin neurogenesis in Drosophila. , 1995, Development.

[10]  M. Jaiswal,et al.  Fat and Wingless signaling oppositely regulate epithelial cell-cell adhesion and distal wing development in Drosophila , 2006, Development.

[11]  G. Morata,et al.  Developmental compartmentalisation of the wing disk of Drosophila. , 1973, Nature: New biology.

[12]  J. Modolell,et al.  The Iroquois homeodomain proteins are required to specify body wall identity in Drosophila. , 1999, Genes & development.

[13]  R. Mann,et al.  Differing strategies for the establishment and maintenance of teashirt and homothorax repression in the Drosophila wing , 2004, Development.

[14]  G. Struhl,et al.  Control of Drosophila wing growth by the vestigial quadrant enhancer , 2007, Development.

[15]  G. Struhl,et al.  Control of growth and patterning of the Drosophila wing imaginal disc by EGFR-mediated signaling. , 2002, Development.

[16]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[17]  P. Lawrence,et al.  Control of compartment development by the engrailed gene in Drosophila , 1975, Nature.

[18]  G M Rubin,et al.  Gene disruptions using P transposable elements: an integral component of the Drosophila genome project. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[19]  A. Simcox,et al.  Dual role for Drosophila epidermal growth factor receptor signaling in early wing disc development. , 2000, Genes & development.

[20]  G. Morata,et al.  Function and regulation of homothorax in the wing imaginal disc of Drosophila. , 2000, Development.

[21]  R. Mann,et al.  A dual role for homothorax in inhibiting wing blade development and specifying proximal wing identities in Drosophila. , 2000, Development.

[22]  N. Perrimon,et al.  Dual functions of wingless in the Drosophila leg imaginal disc. , 1995, Development.

[23]  A. Garcı́a-Bellido,et al.  Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc. , 1996, Development.

[24]  J. Couso,et al.  Serrate and wingless cooperate to induce vestigial gene expression and wing formation in Drosophila , 1995, Current Biology.

[25]  Kirby D. Johnson,et al.  Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic , 1997, Nature.

[26]  K. Basler,et al.  Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. , 1996, Development.

[27]  R. Mann,et al.  The developmental and molecular biology of genes that subdivide the body of Drosophila. , 2000, Annual review of cell and developmental biology.

[28]  J. Couso,et al.  Different mechanisms initiate and maintain wingless expression in the Drosophila wing hinge. , 2002, Development.

[29]  S. Carroll,et al.  Control of Drosophila wing and haltere development by the nuclear vestigial gene product. , 1991, Genes & development.

[30]  G. Struhl,et al.  Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. , 1995, Development.

[31]  S. Cohen,et al.  Repression of Teashirt marks the initiation of wing development. , 2002, Development.

[32]  F. Díaz-Benjumea,et al.  Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. , 1995, Development.

[33]  G. Struhl,et al.  Reading the Hedgehog morphogen gradient by measuring the ratio of bound to unbound Patched protein , 2004, Nature.

[34]  S. Ochoa.  The dachsous gene , a member of the cadherin family , is required for Wg-dependent pattern formation in the Drosophila wing disc , 2022 .

[35]  C. Rauskolb,et al.  Boundaries in development: formation and function. , 2001, Annual review of cell and developmental biology.

[36]  G. Struhl,et al.  Different levels of Ras activity can specify distinct transcriptional and morphological consequences in early Drosophila embryos. , 1997, Development.

[37]  P. Lawrence,et al.  Generation of medial and lateral dorsal body domains by the pannier gene of Drosophila. , 2000, Development.

[38]  M. Hoch,et al.  defective proventriculus is required for pattern formation along the proximodistal axis, cell proliferation and formation of veins in the Drosophila wing , 2003, Development.

[39]  K. Moses,et al.  Role of the EGF receptor pathway in growth and patterning of the Drosophila wing through the regulation of vestigial. , 1999, Development.

[40]  J. Couso,et al.  Proximo-distal development in the legs of Drosophila. , 1998, The International journal of developmental biology.

[41]  W. Brook,et al.  Antagonistic Interactions Between Wingless and Decapentaplegic Responsible for Dorsal-Ventral Pattern in the Drosophila Leg , 1996, Science.

[42]  C. Neumann,et al.  Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. , 1997, Development.

[43]  S M Cohen,et al.  A hierarchy of cross-regulation involving Notch, wingless, vestigial and cut organizes the dorsal/ventral axis of the Drosophila wing. , 1996, Development.

[44]  G. Struhl,et al.  Presenilin-mediated transmembrane cleavage is required for Notch signal transduction in Drosophila. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  A. Garcı́a-Bellido.  Genetic control of wing disc development in Drosophila. , 2008, Ciba Foundation symposium.

[46]  S. Artavanis-Tsakonas,et al.  Cell proliferation control by Notch signaling in Drosophila development. , 1998, Development.

[47]  Konrad Basler,et al.  Organizing activity of wingless protein in Drosophila , 1993, Cell.

[48]  X. Liu,et al.  Roles for scalloped and vestigial in regulating cell affinity and interactions between the wing blade and the wing hinge. , 2000, Developmental biology.

[49]  A. Garcı́a-Bellido,et al.  Genetic requirements of vestigial in the regulation of Drosophila wing development , 2003, Development.

[50]  B. Glick,et al.  Rapidly maturing variants of the Discosoma red fluorescent protein (DsRed) , 2002, Nature Biotechnology.

[51]  S. Cohen,et al.  Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila , 1993, Cell.

[52]  G. Struhl,et al.  Nuclear Access and Action of Notch In Vivo , 1998, Cell.

[53]  S. Carroll,et al.  The Vestigial and Scalloped proteins act together to directly regulate wing-specific gene expression in Drosophila. , 1998, Genes & development.

[54]  J. Modolell,et al.  The Iroquois homeobox genes function as dorsal selectors in the Drosophila head. , 2000, Development.

[55]  G. Struhl,et al.  Subdivision of the Drosophila wing imaginal disc by EGFR-mediated signaling. , 2002, Development.

[56]  S. Blair.  Compartments and appendage development in Drosophila , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[57]  K. Irvine,et al.  Action of fat, four-jointed, dachsous and dachs in distal-to-proximal wing signaling , 2004, Development.

[58]  S. Carroll,et al.  Cell recognition, signal induction, and symmetrical gene activation at the dorsal-ventral boundary of the developing drosophila wing , 1995, Cell.

[59]  John B. Thomas,et al.  The role of apterous in the control of dorsoventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila. , 1994, Development.

[60]  Liqun Luo,et al.  Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development , 2001, Trends in Neurosciences.

[61]  J. Lis,et al.  New heat shock puffs and β=galactosidase activity resulting from transformation of Drosophila with an hsp70-lacZ hybrid gene , 1983, Cell.

[62]  Sean B. Carroll,et al.  Integration of positional signals and regulation of wing formation and identity by Drosophila vestigial gene , 1996, Nature.

[63]  A. Garcı́a-Bellido,et al.  Notch signaling directly controls cell proliferation in the Drosophila wing disc. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[64]  G. Halder,et al.  Selector and signalling molecules cooperate in organ patterning , 2002, Nature cell biology.