Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning

INTERACTION between distinctly specified cells in adjacent compartments establishes organizing centres that control growth and specify cell fate in the developing limbs of Drosophila1–5. Localized expression of the secreted Hedgehog protein (Hh) by cells in the posterior compartment6–8 induces expression of the secreted signalling molecules decapentaplegic (dpp) or wingless (wg) in nearby anterior cells2,3. wg and dpp in turn organize spatial pattern in the wing and leg imaginal discs2,4,9. The Hh signal is thought to act by antagonizing the ability of the patched (ptc) gene product to repress wg and dpp expression10–14. Here we present evidence that removing activity of the gene encoding cyclic AMP-dependent protein kinase A (pka) is functionally equivalent to removing ptc activity or to providing cells with the Hh signal. These findings suggest that cyclic AMP-dependent protein kinase A is a component of the signal transduction pathway through which Hh and Ptc direct localized expression of dpp (or wg) and establish the compartment boundary organizer.

[1]  W. Gelbart,et al.  An extensive 3' cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-beta family in Drosophila. , 1991, Development.

[2]  C. Strader,et al.  Structure and function of G protein-coupled receptors. , 1994, Annual review of biochemistry.

[3]  W. Gelbart,et al.  The relationship of decapentaplegic and engrailed expression in Drosophila imaginal disks: do these genes mark the anterior-posterior compartment boundary? , 1991, Development.

[4]  P. Ingham,et al.  Role of the Drosophila patched gene in positional signalling , 1991, Nature.

[5]  Konrad Basler,et al.  Compartment boundaries and the control of Drosopfiffa limb pattern by hedgehog protein , 1994, Nature.

[6]  T. Tabata,et al.  The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. , 1992, Genes & development.

[7]  G. Rubin,et al.  Analysis of genetic mosaics in developing and adult Drosophila tissues. , 1993, Development.

[8]  I. Kiss,et al.  P-lacW insertional mutagenesis on the second chromosome of Drosophila melanogaster: isolation of lethals with different overgrowth phenotypes. , 1993, Genetics.

[9]  P. Ingham,et al.  The Drosophila segment polarity gene patched is involved in a position-signalling mechanism in imaginal discs. , 1990, Development.

[10]  L. Hartwell,et al.  cAMPing out , 1994, Nature.

[11]  E. Wieschaus,et al.  Segment polarity gene interactions modulate epidermal patterning in Drosophila embryos. , 1993, Development.

[12]  I. Guerrero,et al.  Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. , 1994, The EMBO journal.

[13]  M. Scott,et al.  The Drosophila patched gene encodes a putative membrane protein required for segmental patterning , 1989, Cell.

[14]  D. Kalderon,et al.  RNA localization along the anteroposterior axis of the Drosophila oocyte requires PKA-mediated signal transduction to direct normal microtubule organization. , 1994, Genes & development.

[15]  A. Taylor,et al.  A protein with several possible membrane-spanning domains encoded by the Drosophila segment polarity gene patched , 1989, Nature.

[16]  T. Tabata,et al.  Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs , 1994, Cell.

[17]  P. Beachy,et al.  Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog , 1992, Cell.

[18]  M. Scott,et al.  patched overexpression causes loss of wingless expression in Drosophila embryos. , 1994, Developmental biology.

[19]  P. Simpson,et al.  The segment polarity gene costal-2 in Drosophila. I. The organization of both primary and secondary embryonic fields may be affected. , 1987, Developmental biology.

[20]  P. Ingham.  Localized hedgehog activity controls spatial limits of wingless transcription in the Drosophila embryo , 1993, Nature.

[21]  G. Rubin,et al.  Isolation and characterization of Drosophila cAMP-dependent protein kinase genes. , 1988, Genes & development.

[22]  E. Wieschaus,et al.  fringe, a boundary-specific signaling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development , 1994, Cell.

[23]  E. Sánchez-Herrero,et al.  The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development. , 1994, The EMBO journal.

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

[25]  J. Mohler,et al.  Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila. , 1992, Development.

[26]  Peter N. Devreotes,et al.  G protein-linked signaling pathways control the developmental program of dictyostelium , 1994, Neuron.

[27]  S. Cohen,et al.  Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs , 1994, Nature.