Morphogen gradients. A question of time or concentration?

Morphogens are secreted proteins that organize surrounding tissues into distinct territories and are thought to act as a function of a threshold of their concentration. Although it has been demonstrated that morphogens act directly on the cells and do not rely on secondary signalling relays, intracellular sequential induction mechanisms, which are dependent on a simple signalling instruction, have not been excluded. Here, we present an alternative model to account for the organizing properties of morphogens, and propose that initial exposure to signalling changes cell context, which in combination with continuing morphogen activity, results in the expression of novel targets.

[1]  L Wolpert,et al.  One hundred years of positional information. , 1996, Trends in genetics : TIG.

[2]  T. Lecuit,et al.  Dpp receptor levels contribute to shaping the Dpp morphogen gradient in the Drosophila wing imaginal disc. , 1998, Development.

[3]  S. Cohen,et al.  Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing , 1996, Nature.

[4]  B. Charroux,et al.  Trunk-specific modulation of Wingless signalling in Drosophila by Teashirt binding to Armadillo , 1998, Current Biology.

[5]  G. Struhl,et al.  Direct and Long-Range Action of a DPP Morphogen Gradient , 1996, Cell.

[6]  B. Charroux,et al.  The C‐terminal domain of Armadillo binds to hypophosphorylated Teashirt to modulate Wingless signalling in Drosophila , 1999, The EMBO journal.

[7]  R. Nusse,et al.  Wingless Repression of Drosophila frizzled 2 Expression Shapes the Wingless Morphogen Gradient in the Wing , 1998, Cell.

[8]  L. Wolpert.  Positional information revisited. , 1989, Development.

[9]  R. Nusse,et al.  Mechanisms of Wnt signaling in development. , 1998, Annual review of cell and developmental biology.

[10]  G. Campbell,et al.  Transducing the Dpp Morphogen Gradient in the Wing of Drosophila Regulation of Dpp Targets by brinker , 1999, Cell.

[11]  K. Van Nimmen,et al.  Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A , 1990, Nature.

[12]  J. Gurdon,et al.  Direct and continuous assessment by cells of their position in a morphogen gradient , 1995, Nature.

[13]  E. Wieschaus,et al.  The Drosophila Gene brinker Reveals a Novel Mechanism of Dpp Target Gene Regulation , 1999, Cell.

[14]  J. Slack.  Morphogenetic gradients — past and present , 1987 .

[15]  T. Kornberg,et al.  Cytonemes Cellular Processes that Project to the Principal Signaling Center in Drosophila Imaginal Discs , 1999, Cell.

[16]  Ken W. Y. Cho,et al.  Interaction of goosecoid and brachyury in Xenopus mesoderm patterning , 1997, Mechanisms of Development.

[17]  G. Morata,et al.  The homeobox gene Distal-less induces ventral appendage development in Drosophila. , 1997, Genes & development.

[18]  J. Massagué.  TGF-beta signal transduction. , 1998, Annual review of biochemistry.

[19]  Bernard Jacq,et al.  The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs , 1991, Cell.

[20]  R. Derynck,et al.  Transcriptional Activators of TGF-β Responses: Smads , 1998, Cell.

[21]  J. Smith,et al.  Responses of embryonic xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm , 1992, Cell.

[22]  P. Lemaire,et al.  Activin signalling and response to a morphogen gradient , 1994, Nature.

[23]  P. Lawrence.  Gradients in the Insect Segment: The Orientation of Hairs in the Milkweed Bug Oncopeltus Fasciatus , 1966 .

[24]  H. Spemann.  Embryonic development and induction , 1938 .

[25]  J. Smith,et al.  Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate , 1990, Nature.

[26]  H. F. STUMPF,et al.  Mechanism by which Cells estimate their Location within the Body , 1966, Nature.

[27]  J. Gurdon,et al.  A quantitative analysis of signal transduction from activin receptor to nucleus and its relevance to morphogen gradient interpretation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  G. Campbell,et al.  The roles of the homeobox genes aristaless and Distal-less in patterning the legs and wings of Drosophila. , 1998, Development.

[29]  T. Klein,et al.  The vestigial gene product provides a molecular context for the interpretation of signals during the development of the wing in Drosophila. , 1999, Development.

[30]  S. Cohen,et al.  Problems and paradigms: Morphogens and pattern formation , 1997 .

[31]  G. Struhl,et al.  Direct and Long-Range Action of a Wingless Morphogen Gradient , 1996, Cell.

[32]  A. Turing.  The chemical basis of morphogenesis , 1952, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.

[33]  Ken W. Y. Cho,et al.  Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid , 1991, Cell.

[34]  T. Tabata,et al.  brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes , 1999, Nature.

[35]  J. Gurdon,et al.  Cells’ Perception of Position in a Concentration Gradient , 1998, Cell.