Direct and continuous assessment by cells of their position in a morphogen gradient

ACCORDING to the morphogen gradient concept1á¤-5, cells in one part of an embryo secrete diffusible molecules (morphogens) that spread to other nearby cells and activate genes at different threshold concentrations. Strong support for the operation of a morphogen gradient mechanism in vertebrate development has come from the biochemical experiments of Green and Smith6,7, who induced different kinds of gene expression in amphibian blastula cells exposed to small changes in activin concentration. But the interpretation of these experiments has been complicated by recent reports8á¤-10 that cells tested for gene expression 3 hours after exposure to activin fail to show the graded response previously reported at 15 hours6,7, a result suggesting that cells recognize their position in a gradient by an indirect mechanism. Here we conclude from the in situ analysis of blastula tissue containing activin-loaded beads11 that cells respond directly to changing morphogen concentrations, in a way that resembles a ratchet-like process.

[1]  L. Dale,et al.  Effects of truncated activin and FGF receptors and of follistatin on the inducing activities of BVg1 and activin: does activin play a role in mesoderm induction? , 1994, The EMBO journal.

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

[3]  P. Lawrence Background to bicoid , 1988, Cell.

[4]  Jonathan M.W. Slack,et al.  From egg to embryo : regional specification in early development , 1991 .

[5]  E. Jones,et al.  The development of animal cap cells in Xenopus: a measure of the start of animal cap competence to form mesoderm , 1987 .

[6]  P. D. Vize,et al.  Vg1 and regional specification in vertebrates: a new role for an old molecule. , 1994, Trends in genetics : TIG.

[7]  M. Mercola,et al.  Morphological differences in Xenopus embryonic mesodermal cells are specified as an early response to distinct threshold concentrations of activin. , 1994, Development.

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

[9]  D. Melton,et al.  Processed Vg1 protein is an axial mesoderm inducer in xenopus , 1993, Cell.

[10]  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.

[11]  K. Anderson,et al.  decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo , 1992, Cell.

[12]  J. Slack From Egg to Embryo , 1983 .

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

[14]  J. Gurdon,et al.  Activation of muscle-specific actin genes in xenopus development by an induction between animal and vegetal cells of a blastula , 1985, Cell.

[15]  Michael Levine,et al.  Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen , 1993, Cell.

[16]  Douglas A. Melton,et al.  Mesodermal patterning by an inducer gradient depends on secondary cell–cell communication , 1994, Current Biology.

[17]  J. Smith,et al.  Slow emergence of a multithreshold response to activin requires cell-contact-dependent sharpening but not prepattern. , 1994, Development.

[18]  James C. Smith,et al.  Gastrulation movements provide an early marker of mesoderm induction in Xenopus laevis , 1987 .

[19]  C. Tickle,et al.  Morphogens in chick limb development , 1989, Bioessays.

[20]  J. Smith,et al.  Expression of a xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction , 1991, Cell.

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

[22]  J. Cooke,et al.  Morphogens in vertebrate development: how do they work? , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.