Polarity determination in the Drosophila eye: a novel role for unpaired and JAK/STAT signaling.

The JAK/STAT signaling pathway is required for many processes including cytokine signaling, hematopoiesis, gliagenesis, and Drosophila segmentation. In this report we present evidence demonstrating that the JAK/STAT pathway is also central to the establishment of planar polarity during Drosophila eye development. We show that a localized source of the pathway ligand, Unpaired, is present at the midline of the developing eye, which is capable of activating the JAK/STAT pathway over long distances. A gradient of JAK/STAT activity across the DV axis of the eye regulates ommatidial polarity via an unidentified second signal. Additionally, localized Unpaired influences the position of the equator via repression of mirror.

[1]  K. Moses,et al.  A polarity field is established early in the development of the Drosophila compound eye , 1997, Mechanisms of Development.

[2]  K. White,et al.  Characterization and spatial distribution of the ELAV protein during Drosophila melanogaster development. , 1991, Journal of neurobiology.

[3]  M. Brodsky,et al.  mirror encodes a novel PBX-class homeoprotein that functions in the definition of the dorsal-ventral border in the Drosophila eye. , 1997, Genes & development.

[4]  P. O’Farrell,et al.  A nuclear GFP that marks nuclei in living Drosophila embryos; maternal supply overcomes a delay in the appearance of zygotic fluorescence. , 1995, Developmental biology.

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

[6]  S. Lindquist,et al.  The FLP recombinase of yeast catalyzes site-specific recombination in the drosophila genome , 1989, Cell.

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

[8]  P. Adler,et al.  A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains , 1989, Nature.

[9]  J. Darnell,et al.  Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. , 1992, Science.

[10]  Marek Mlodzik,et al.  Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye , 1999, Nature.

[11]  M. Bate,et al.  The development of Drosophila melanogaster , 1993 .

[12]  Norbert Perrimon,et al.  marelle Acts Downstream of the Drosophila HOP/JAK Kinase and Encodes a Protein Similar to the Mammalian STATs , 1996, Cell.

[13]  H. Luo,et al.  An amino acid substitution in the Drosophila hopTum‐l Jak kinase causes leukemia‐like hematopoietic defects. , 1995, The EMBO journal.

[14]  H. Luo,et al.  A JAK-STAT pathway regulates wing vein formation in Drosophila. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Wehrli,et al.  Independent regulation of anterior/posterior and equatorial/polar polarity in the Drosophila eye; evidence for the involvement of Wnt signaling in the equatorial/polar axis. , 1998, Development.

[16]  N. Perrimon,et al.  l(1)hopscotch, A larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila. , 1986, Developmental biology.

[17]  N. Perrimon,et al.  Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway. , 1998, Genes & development.

[18]  Kwang-Wook Choi,et al.  Fringe is essential for mirror symmetry and morphogenesis in the Drosophila eye , 1998, Nature.

[19]  D. Levy,et al.  Targeted Disruption of the Mouse Stat1 Gene Results in Compromised Innate Immunity to Viral Disease , 1996, Cell.

[20]  C. Doe,et al.  The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. , 1995, Development.

[21]  U. Heberlein,et al.  Role of the morphogenetic furrow in establishing polarity in the Drosophila eye. , 1995, Development.

[22]  K. Moses,et al.  Wingless and patched are negative regulators of the morphogenetic furrow and can affect tissue polarity in the developing Drosophila compound eye. , 1995, Development.

[23]  H. Steller,et al.  Positional information along the dorsal-ventral axis of the Drosophila eye: graded expression of the four-jointed gene. , 1996, Developmental biology.

[24]  G. Rubin,et al.  Ellipse mutations in the Drosophila homologue of the EGF receptor affect pattern formation, cell division, and cell death in eye imaginal discs. , 1992, Developmental biology.

[25]  J. Johnston,et al.  Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID) , 1995, Nature.

[26]  N. Perrimon,et al.  Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. , 1995, The EMBO journal.

[27]  M. Kraus,et al.  Characterization of a Stat-like DNA Binding Activity in Drosophila melanogaster(*) , 1995, The Journal of Biological Chemistry.

[28]  S. Bray,et al.  Frizzled regulation of Notch signalling polarizes cell fate in the  Drosophila eye , 1999, Nature.

[29]  Claude Desplan,et al.  Identification of a Stat Gene That Functions in Drosophila Development , 1996, Cell.

[30]  D. Ready,et al.  Neuronal differentiation in Drosophila ommatidium. , 1987, Developmental biology.

[31]  J. Zhang,et al.  frizzled regulates mirror-symmetric pattern formation in the Drosophila eye. , 1995, Development.

[32]  S. Benzer,et al.  Independent determination of symmetry and polarity in the Drosophila eye. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  L. Hennighausen,et al.  Stat5a is mandatory for adult mammary gland development and lactogenesis. , 1997, Genes & development.

[34]  D. Strutt,et al.  Ommatidial polarity in the Drosophila eye is determined by the direction of furrow progression and local interactions. , 1995, Development.

[35]  M. Greenberg,et al.  Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. , 1997, Science.

[36]  M. Kaplan,et al.  Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice , 1996, Nature.

[37]  J. Darnell.  STATs and gene regulation. , 1997, Science.

[38]  C. Rauskolb,et al.  Dorsal-ventral signaling in the Drosophila eye. , 1998, Science.

[39]  J. O’Shea.  Jaks, STATs, cytokine signal transduction, and immunoregulation: are we there yet? , 1997, Immunity.

[40]  D. Yamamoto,et al.  The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. , 1997, Development.

[41]  M. Dominguez,et al.  A dorsal/ventral boundary established by Notch controls growth and polarity in the Drosophila eye , 1998, Nature.

[42]  U. Heberlein,et al.  Dorsoventral patterning in the Drosophila retina by wingless. , 1998, Development.

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

[44]  W. Paul,et al.  Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted State6 gene , 1996, Nature.

[45]  G M Rubin,et al.  wingless inhibits morphogenetic furrow movement in the Drosophila eye disc. , 1995, Development.

[46]  N. Perrimon,et al.  Stripe-specific regulation of pair-rule genes by hopscotch, a putative Jak family tyrosine kinase in Drosophila. , 1994, Genes & development.