Short-Range Signaling by Candidate Morphogens of the TGFβ Family and Evidence for a Relay Mechanism of Induction

The specification and patterning of cell fates by a morphogen gradient is a unifying theme of developmental biology, yet little evidence exists for the presence of gradients in vivo or to show how such putative gradients form. Vg1 and activin are candidate morphogens involved in Xenopus mesoderm induction. This study suggests that these TGF beta family members act on adjacent cells but do not travel through the intact extracellular space to induce distant cells directly. Moreover, we present evidence for the presence of secondary inducing signals that could be involved in relaying signals to distant cells. These results suggest that if a localized cellular source of an inducer acts to pattern mesodermal cells at a distance in Xenopus embryos, it does so by a relay mechanism.

[1]  C. Kenyon.  A perfect vulva every time: Gradients and signaling cascades in C. elegans , 1995, Cell.

[2]  Iman H. Brivanlou,et al.  TGF-beta signals and a pattern in Xenopus laevis endodermal development. , 1996, Development.

[3]  J. Brockes,et al.  Monoclonal antibodies identify blastemal cells derived from dedifferentiating muscle in newt limb regeneration , 1984, Nature.

[4]  S. Sokol,et al.  Heparan sulfate proteoglycans are required for mesoderm formation in Xenopus embryos. , 1994, Development.

[5]  J. Slack.  The nature of the mesoderm-inducing signal in Xenopus: a transfilter induction study. , 1991, Development.

[6]  J. Gerhart,et al.  Blastomere derivation and domains of gene expression in the Spemann Organizer of Xenopus laevis. , 1995, Development.

[7]  Thomas R Clandinin,et al.  Different Levels of the C. elegans growth factor LIN-3 promote distinct vulval precursor fates , 1995, Cell.

[8]  D. Melton,et al.  Induction of dorsal mesoderm by soluble, mature Vg1 protein. , 1995, Development.

[9]  J M Slack,et al.  Fate map for the 32-cell stage of Xenopus laevis. , 1987, Development.

[10]  L. Wolpert.  Positional information and the spatial pattern of cellular differentiation. , 1969, Journal of theoretical biology.

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

[12]  A. Brivanlou,et al.  Expression of an engrailed-related protein is induced in the anterior neural ectoderm of early Xenopus embryos. , 1989, Development.

[13]  Pattern Formation: Hedgehog points the way , 1994, Current Biology.

[14]  J. Massagué,et al.  Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-β receptor system , 1991, Cell.

[15]  D. Melton,et al.  Inhibition of activin receptor signaling promotes neuralization in Xenopus , 1994, Cell.

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

[17]  Y. Ohshima,et al.  Mosaic analysis of the let-23 gene function in vulval induction of Caenorhabditis elegans. , 1995, Development.

[18]  M. R. Kalt.  The relationship between cleavage and blastocoel formation in Xenopus laevis. II. Electron microscopic observations. , 1971, Journal of embryology and experimental morphology.

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

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

[21]  J. Slack,et al.  Mesoderm induction by the mesoderm of Xenopus neurulae. , 1989, The International journal of developmental biology.

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

[23]  E. Ruoslahti,et al.  Negative regulation of transforming growth factor-β by the proteoglycan decorin , 1990, Nature.

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

[25]  D. Melton,et al.  Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity , 1994, Cell.

[26]  D. Melton,et al.  Expression of activin mRNA during early development in Xenopus laevis. , 1993, Developmental biology.

[27]  Peng Hb.  Xenopus laevis: Practical uses in cell and molecular biology. Solutions and protocols. , 1991, Methods in cell biology.

[28]  P. Lemaire,et al.  A role for cytoplasmic determinants in mesoderm patterning: cell-autonomous activation of the goosecoid and Xwnt-8 genes along the dorsoventral axis of early Xenopus embryos. , 1994, Development.

[29]  M. Whitman,et al.  Mesoderm induction by activin requires FGF-mediated intracellular signals. , 1994, Development.

[30]  H. Okamoto,et al.  bFGF as a possible morphogen for the anteroposterior axis of the central nervous system in Xenopus. , 1995, Development.

[31]  C. Nüsslein-Volhard,et al.  The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner , 1988, Cell.

[32]  H. Lodish,et al.  The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm , 1994, Molecular and cellular biology.

[33]  Jim Smith.  How to tell a cell where it is , 1996, Nature.

[34]  J C Smith,et al.  The organization of mesodermal pattern in Xenopus laevis: experiments using a Xenopus mesoderm-inducing factor. , 1987, Development.

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

[36]  D. Melton,et al.  Hormonal regulation of embryogenesis: the formation of mesoderm in Xenopus laevis. , 1994, Endocrine reviews.

[37]  A. Colman,et al.  Secretion and mesoderm‐inducing activity of the TGF‐beta‐related domain of Xenopus Vg1. , 1993, The EMBO journal.

[38]  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.

[39]  R. Weinberg,et al.  Expression cloning of the TGF-β type II receptor, a functional transmembrane serine/threonine kinase , 1992, Cell.

[40]  J. Graff,et al.  Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo , 1994, Cell.

[41]  A. Roberts,et al.  cDNA cloning of porcine transforming growth factor-beta 1 mRNAs. Evidence for alternate splicing and polyadenylation. , 1988, The Journal of biological chemistry.

[42]  H. Peng.  Solutions and protocols , 1991 .

[43]  J. Smith,et al.  Growth factors as morphogens: do gradients and thresholds establish body plan? , 1991, Trends in genetics : TIG.

[44]  S. Moody,et al.  The cleavage stage origin of Spemann's Organizer: analysis of the movements of blastomere clones before and during gastrulation in Xenopus. , 1994, Development.

[45]  T. Musci,et al.  FGF is a prospective competence factor for early activin-type signals in Xenopus mesoderm induction. , 1995, Development.

[46]  C. Wright,et al.  Autonomous endodermal determination in Xenopus: regulation of expression of the pancreatic gene XlHbox 8. , 1995, Developmental biology.

[47]  A. Colman,et al.  Developmental expression of the protein product of Vg1, a localized maternal mRNA in the frog Xenopus laevis. , 1989, The EMBO journal.

[48]  D. Kimelman,et al.  Activin-mediated mesoderm induction requires FGF. , 1994, Development.

[49]  D. Melton,et al.  Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. , 1984, Nucleic acids research.

[50]  S. K. Kirn,et al.  Sequential signalling during Caenorhabditis elegans vulval induction , 1995, Nature.

[51]  Jeffrey D. Esko,et al.  Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor , 1991, Cell.

[52]  D. Melton,et al.  Localized synthesis of the Vg1 protein during early Xenopus development. , 1989, Development.

[53]  D. Melton,et al.  A mouse macrophage factor induces head structures and organizes a body axis in Xenopus. , 1990, Science.

[54]  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.

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

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

[57]  H. Sive,et al.  The frog prince-ss: a molecular formula for dorsoventral patterning in Xenopus. , 1993, Genes & development.

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

[59]  D. Ejima,et al.  Presence of activin (erythroid differentiation factor) in unfertilized eggs and blastulae of Xenopus laevis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.