Hedgehog and Wingless stabilize but do not induce cell fate during Drosophila dorsal embryonic epidermal patterning

A fundamental concept in development is that secreted molecules such as Wingless (Wg) and Hedgehog (Hh) generate pattern by inducing cell fate. By following markers of cellular identity posterior to the Wg- and Hh-expressing cells in the Drosophila dorsal embryonic epidermis, we provide evidence that neither Wg nor Hh specifies the identity of the cell types they pattern. Rather, they maintain pre-existing cellular identities that are otherwise unstable and progress stepwise towards a default fate. Wg and Hh therefore generate pattern by inhibiting specific switches in cell identity, showing that the specification and the patterning of a given cell are uncoupled. Sequential binary decisions without induction of cell identity give rise to both the groove cells and their posterior neighbors. The combination of independent progression of cell identity and arrest of progression by signals facilitates accurate patterning of an extremely plastic developing epidermis.

[1]  J. Vonesch,et al.  Glide directs glial fate commitment and cell fate switch between neurones and glia. , 1996, Development.

[2]  I. Weissman,et al.  Wnt proteins are lipid-modified and can act as stem cell growth factors , 2003, Nature.

[3]  P. O’Farrell,et al.  The engrailed locus of drosophila: In situ localization of transcripts reveals compartment-specific expression , 1985, Cell.

[4]  H. Krause,et al.  Dynamic changes in the functions of Odd-skipped during early Drosophila embryogenesis. , 1998, Development.

[5]  C. Alexandre,et al.  Wingless and Hedgehog pattern Drosophila denticle belts by regulating the production of short-range signals. , 1999, Development.

[6]  I. Weissman,et al.  A role for Wnt signalling in self-renewal of haematopoietic stem cells , 2003, Nature.

[7]  B. Porse,et al.  Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block , 2006, Nature Immunology.

[8]  P. Lawrence,et al.  Borders of parasegments in Drosophila embryos are delimited by the fushi tarazu and even-skipped genes , 1987, Nature.

[9]  A. Laughon,et al.  Ftz-F1 is a cofactor in Ftz activation of the Drosophila engrailed gene. , 1997, Development.

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

[11]  N. Perrimon,et al.  Zygotic lethal mutations with maternal effect phenotypes in Drosophila melanogaster. II. Loci on the second and third chromosomes identified by P-element-induced mutations. , 1996, Genetics.

[12]  E. Wieschaus,et al.  Gene activities and segmental patterning in Drosophila: analysis of odd-skipped and pair-rule double mutants. , 1988, Genes & development.

[13]  Richard D Fetter,et al.  glial cells missing: a genetic switch that controls glial versus neuronal fate , 1995, Cell.

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

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

[16]  S. Tsukita,et al.  Dynamic features of adherens junctions during Drosophila embryonic epithelial morphogenesis revealed by a Dα-catenin-GFP fusion protein , 1999, Development Genes and Evolution.

[17]  N E Baker,et al.  Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos , 1987, The EMBO journal.

[18]  F. Rosenbauer,et al.  Hematopoietic stem cell and multilineage defects generated by constitutive beta-catenin activation. , 2006, Nature immunology.

[19]  E. Wieschaus,et al.  Molecular analysis of odd‐skipped, a zinc finger encoding segmentation gene with a novel pair‐rule expression pattern. , 1990, The EMBO journal.

[20]  U. Tepass,et al.  crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia , 1990, Cell.

[21]  R. B. Green,et al.  The Drumstick/Lines/Bowl regulatory pathway links antagonistic Hedgehog and Wingless signaling inputs to epidermal cell differentiation. , 2005, Genes & development.

[22]  W. Gehring,et al.  Localized expression of sloppy paired protein maintains the polarity of Drosophila parasegments. , 1994, Genes & development.

[23]  E. Knust,et al.  Drosophila Atypical Protein Kinase C Associates with Bazooka and Controls Polarity of Epithelia and Neuroblasts , 2000, The Journal of cell biology.

[24]  Judith A. Mack,et al.  naked cuticle encodes an inducible antagonist of Wnt signalling , 2000, Nature.

[25]  P. Ingham,et al.  Genetic analysis of hedgehog signalling in the Drosophila embryo. , 1993, Development (Cambridge, England). Supplement.

[26]  N E Baker,et al.  Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo. , 1988, Development.

[27]  P. Lawrence,et al.  Parasegments and compartments in the Drosophila embryo , 1985, Nature.

[28]  Alfonso Martinez Arias,et al.  Filtering transcriptional noise during development: concepts and mechanisms , 2006, Nature Reviews Genetics.

[29]  N. Perrimon,et al.  Cell patterning in the Drosophila segment: engrailed and wingless antigen distributions in segment polarity mutant embryos. , 1993, Development.

[30]  H. Jäckle,et al.  Drosophila segment borders result from unilateral repression of hedgehog activity by wingless signaling. , 2000, Molecular cell.

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

[32]  Judith A. Kassis,et al.  Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis , 1988, Nature.

[33]  W. McGinnis,et al.  Isolation of a homoeo box-containing gene from the engrailed region of Drosophila and the spatial distribution of its transcripts , 1985, Nature.

[34]  N. Perrimon,et al.  Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. , 1989, Genetics.

[35]  P. Ingham,et al.  Isolation, structure, and expression of even-skipped: A second pair-rule gene of Drosophila containing a homeo box , 1986, Cell.

[36]  H. Spemann,et al.  über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren , 1924, Archiv für mikroskopische Anatomie und Entwicklungsmechanik.

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

[38]  T. Hosoya,et al.  Glial cells missing: A binary switch between neuronal and glial determination in drosophila , 1995, Cell.

[39]  P. O’Farrell,et al.  Establishment and refinement of segmental pattern in the Drosophila embryo: spatial control of engrailed expression by pair-rule genes. , 1987, Genes & development.

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

[41]  Gerald M Rubin,et al.  Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway , 1995, Cell.

[42]  M. Peifer,et al.  Abelson kinase regulates epithelial morphogenesis in Drosophila , 2001, The Journal of cell biology.

[43]  C. Alexandre,et al.  Segment boundary formation in Drosophila embryos , 2003, Development.

[44]  G. Struhl,et al.  Dual Roles for Patched in Sequestering and Transducing Hedgehog , 1996, Cell.