Mutual Regulation ofdecapentaplegicandhedgehogduring the Initiation of Differentiation in theDrosophilaRetina

Abstract Neuronal differentiation in the Drosophila retinal primordium, the eye imaginal disc, begins at the posterior tip of the disc and progresses anteriorly as a wave. The morphogenetic furrow (MF) marks the boundary between undifferentiated anterior cells and differentiating posterior cells. Anterior progression of differentiation is driven by Hedgehog, synthesized by cells located posterior to the MF. We report here that hedgehog ( hh ), which is expressed prior to the start of differentiation along the disc's posterior margin, also plays a crucial role in the initiation of differentiation. Using a temperature-sensitive allele we show that hh is normally required at the posterior margin to maintain the expression of decapentaplegic ( dpp ) and of the proneural gene atonal. In addition, we find that ectopic differentiation driven by ectopic dpp expression or loss of wingless function requires hh. Consistent with this is our observation that ectopic dpp induces the expression of hh along the anterior margin even in the absence of differentiation. Taken together, these data reveal a novel positive regulatory loop between dpp and hh that is essential for the initiation of differentiation in the eye disc.

[1]  U. Heberlein,et al.  Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina. , 1997, Development.

[2]  A. Tomlinson.  The cellular dynamics of pattern formation in the eye of Drosophila. , 1985, Journal of embryology and experimental morphology.

[3]  Yves Grau,et al.  atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system , 1993, Cell.

[4]  S. Zipursky,et al.  The Eye-Specification Proteins So and Eya Form a Complex and Regulate Multiple Steps in Drosophila Eye Development , 1997, Cell.

[5]  J. O'Tousa,et al.  sine oculis is a homeobox gene required for Drosophila visual system development. , 1994, Genetics.

[6]  E. Hafen,et al.  Hedgehog directly controls initiation and propagation of retinal differentiation in the Drosophila eye. , 1997, Genes & development.

[7]  V. Hartenstein,et al.  The drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system , 1994, Neuron.

[8]  K. Basler,et al.  Hedgehog-dependent patterning in the Drosophila eye can occur in the absence of Dpp signaling. , 1996, Developmental biology.

[9]  G. Rubin,et al.  cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in drosophila imaginal discs , 1995, Cell.

[10]  W. Gehring,et al.  Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. , 1994, Science.

[11]  F. Hoffmann,et al.  Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal disks is regulated by 3' cis-regulatory elements. , 1990, Genes & development.

[12]  G. Rubin,et al.  dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. , 1994, Development.

[13]  D. Strutt,et al.  Hedgehog is an indirect regulator of morphogenetic furrow progression in the Drosophila eye disc. , 1997, Development.

[14]  G. Mardon,et al.  Dachshund and Eyes Absent Proteins Form a Complex and Function Synergistically to Induce Ectopic Eye Development in Drosophila , 1997, Cell.

[15]  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.

[16]  K. Basler,et al.  Hedgehog signaling in Drosophila eye and limb development — conserved machinery, divergent roles? , 1997, Current Opinion in Neurobiology.

[17]  S. Selleck,et al.  Regulation of Cell Cycle Synchronization by decapentaplegic During Drosophila Eye Development , 1997, Science.

[18]  G. Rubin,et al.  The homeo domain protein rough is expressed in a subset of cells in the developing Drosophila eye where it can specify photoreceptor cell subtype. , 1990, Genes & development.

[19]  S. Zipursky,et al.  Induction of Drosophila eye development by decapentaplegic. , 1997, Development.

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

[21]  U. Heberlein,et al.  Eye development in Drosophila: formation of the eye field and control of differentiation. , 1998, Current topics in developmental biology.

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

[23]  C. Desplan,et al.  Eye Development: Governed by a Dictator or a Junta? , 1997, Cell.

[24]  N. Patel,et al.  Differential splicing generates a nervous system—Specific form of drosophila neuroglian , 1990, Neuron.

[25]  M. Noll,et al.  The Drosophila smoothened Gene Encodes a Seven-Pass Membrane Protein, a Putative Receptor for the Hedgehog Signal , 1996, Cell.

[26]  S. Benzer,et al.  Development of the Drosophila retina, a neurocrystalline lattice. , 1976, Developmental biology.

[27]  U. Heberlein,et al.  Mechanisms of drosophila retinal morphogenesis: The virtues of being progressive , 1995, Cell.

[28]  G. Mardon,et al.  Ectopic eye development in Drosophila induced by directed dachshund expression. , 1997, Development.

[29]  D. Strutt,et al.  Regulation of furrow progression in the Drosophila eye by cAMP-dependent protein kinase A , 1995, Nature.

[30]  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.

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

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

[33]  P. Ingham,et al.  smoothened encodes a receptor-like serpentine protein required for hedgehog signalling , 1996, Nature.

[34]  T. Lecuit,et al.  Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye. , 1996, Development.

[35]  N. Bonini,et al.  The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. , 1997, Development.

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

[37]  A. Brand,et al.  Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[38]  J. Royet,et al.  Establishing primordia in the Drosophila eye-antennal imaginal disc: the roles of decapentaplegic, wingless and hedgehog. , 1997, Development.

[39]  Y Sun,et al.  Role of the proneural gene, atonal, in formation of Drosophila chordotonal organs and photoreceptors. , 1995, Development.

[40]  M. Wehrli,et al.  Epithelial planar polarity in the developing Drosophila eye. , 1995, Development.

[41]  T. J. Donohoe,et al.  Growth and differentiation in the Drosophila eye coordinated by hedgehog , 1995, Nature.

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

[43]  Seymour Benzer,et al.  The eyes absent gene: Genetic control of cell survival and differentiation in the developing Drosophila eye , 1993, Cell.

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

[45]  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.

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

[47]  Yuh Nung Jan,et al.  atonal is the proneural gene for Drosophila photoreceptors , 1994, Nature.