Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development

Reduced protein kinase A (PKA) activity in anterior imaginal disc cells leads to cell-autonomous induction of decapentaplegic (dpp), wingless (wg), and patched (ptc) transcription that is independent of hedgehog (hh) gene activity. The resulting nonautonomous adult wing and leg pattern duplications are largely due to induced dpp and wg expression and resemble phenotypes elicited by ectopic hh expression. Inhibition of PKA in anterior cells close to the posterior compartment can substitute for hh activity to promote growth of imaginal discs, whereas overexpression of PKA can counteract transcriptional induction of ptc by hh in these cells. PKA therefore appears to be an integral component of the mechanism by which hh regulates the expression of key patterning molecules in imaginal discs.

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

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

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

[4]  D. Kalderon,et al.  Genetic investigation of cAMP-dependent protein kinase function in Drosophila development. , 1993, Genes & development.

[5]  A. Mccarthy.  Development , 1996, Current Opinion in Neurobiology.

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

[7]  M. Bate,et al.  A wingless-dependent polar coordinate system in Drosophila imaginal discs. , 1993, Science.

[8]  D. Lindsley,et al.  The Genome of Drosophila Melanogaster , 1992 .

[9]  K. Moses,et al.  The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye , 1993, Cell.

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

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

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

[13]  J. Whittle.  Pattern formation in imaginal discs. , 1990, Seminars in cell biology.

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

[15]  J. Campos-Ortega,et al.  The basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes , 1994, Cell.

[16]  M. Seldin,et al.  Products, genetic linkage and limb patterning activity of a murine hedgehog gene. , 1994, Development.

[17]  P. Ingham,et al.  A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos , 1993, Cell.

[18]  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.

[19]  N. Perrimon,et al.  Altering the insertional specificity of a Drosophila transposable element. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[20]  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.

[21]  S. DiNardo,et al.  Drosophila hedgehog acts as a morphogen in cellular patterning , 1994, Cell.

[22]  A. Simcox,et al.  Allocation of the thoracic imaginal primordia in the Drosophila embryo. , 1993, Development.

[23]  V. French,et al.  Pattern regulation in epimorphic fields. , 1976, Science.

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

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

[26]  C. Tabin,et al.  Sonic hedgehog mediates the polarizing activity of the ZPA , 1993, Cell.

[27]  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.

[28]  J. Mohler.  Requirements for hedgehog, a segmental polarity gene, in patterning larval and adult cuticle of Drosophila. , 1988, Genetics.

[29]  H. L. Carson,et al.  The Genetics and Biology of Drosophila , 1976, Heredity.

[30]  G. McKnight,et al.  Mutations in the catalytic subunit of cAMP-dependent protein kinase result in unregulated biological activity. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

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

[32]  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.

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

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

[35]  I. Guerrero,et al.  Unrestricted expression of the Drosophila gene patched allows a normal segment polarity , 1991, Nature.

[36]  Ronald L. Davis,et al.  Preferential expression in mushroom bodies of the catalytic subunit of protein kinase A and its role in learning and memory , 1993, Neuron.

[37]  A. Taylor,et al.  Contrasting distributions of patched and hedgehog proteins in the Drosophila embryo , 1993, Mechanisms of Development.

[38]  Gerald M. Rubin,et al.  The TGFβ homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina , 1993, Cell.

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

[40]  C. Nüsslein-Volhard,et al.  Mutations affecting segment number and polarity in Drosophila , 1980, Nature.

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

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

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

[44]  T. Jessell,et al.  Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord , 1994, Cell.

[45]  E. Krebs,et al.  Purification and Characterization of a Protein Inhibitor of Adenosine 3',5'-Monophosphate-dependent Protein Kinases , 1971 .

[46]  Andrew P. McMahon,et al.  Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity , 1993, Cell.

[47]  A. Hannah-Alava.  Morphology and chaetotaxy of the legs of Drosophila melanogaster , 1958 .

[48]  H. Meinhardt.  Cell determination boundaries as organizing regions for secondary embryonic fields. , 1983, Developmental biology.

[49]  T. Weaver,et al.  Axis specification in the developing Drosophila appendage: The role of wingless, decapentaplegic, and the homeobox gene aristaless , 1993, Cell.

[50]  A. Gilman,et al.  G proteins. , 1992, Trends in biochemical sciences.

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

[52]  N. Baker.  Transcription of the segment-polarity gene wingless in the imaginal discs of Drosophila, and the phenotype of a pupal-lethal wg mutation. , 1988, Development.

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