FGF signalling: diverse roles during early vertebrate embryogenesis

Fibroblast growth factor (FGF) signalling has been implicated during several phases of early embryogenesis, including the patterning of the embryonic axes, the induction and/or maintenance of several cell lineages and the coordination of morphogenetic movements. Here, we summarise our current understanding of the regulation and roles of FGF signalling during early vertebrate development.

[1]  R. Patient,et al.  Analysis of FGF function in normal and no tail zebrafish embryos reveals separate mechanisms for formation of the trunk and the tail. , 1995, Development.

[2]  V. Papaioannou,et al.  Paracrine action of FGF4 during periimplantation development maintains trophectoderm and primitive endoderm , 2003, Genesis.

[3]  P. Lemaire,et al.  Neural induction in Xenopus requires early FGF signalling in addition to BMP inhibition , 2005, Development.

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

[5]  Stephen S. Gisselbrecht,et al.  heartless encodes a fibroblast growth factor receptor (DFR1/DFGF-R2) involved in the directional migration of early mesodermal cells in the Drosophila embryo. , 1996, Genes & development.

[6]  E. Amaya,et al.  C/EBPalpha initiates primitive myelopoiesis in pluripotent embryonic cells. , 2009, Blood.

[7]  P. Yelick,et al.  Roles for fgf8 signaling in left-right patterning of the visceral organs and craniofacial skeleton. , 2005, Developmental biology.

[8]  Y. Sasai,et al.  Endoderm induction by the organizer‐secreted factors chordin and noggin in Xenopus animal caps. , 1996, The EMBO journal.

[9]  A. Hemmati-Brivanlou,et al.  Caudalization of neural fate by tissue recombination and bFGF. , 1995, Development.

[10]  Austin G Smith,et al.  Capturing Pluripotency , 2008, Cell.

[11]  Robert Opoka,et al.  FGF signaling is necessary for establishing gut tube domains alongthe anterior–posterior axis in vivo , 2006, Mechanisms of Development.

[12]  M. Nieto,et al.  Neural induction in whole chick embryo cultures by FGF. , 1998, Developmental biology.

[13]  D. Ornitz,et al.  FGFs, heparan sulfate and FGFRs: complex interactions essential for development. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  P. Leder,et al.  Murine FGFR-1 is required for early postimplantation growth and axial organization. , 1994, Genes & development.

[15]  Shaun K Olsen,et al.  Structural basis for fibroblast growth factor receptor activation. , 2005, Cytokine & growth factor reviews.

[16]  H. Weintraub,et al.  Identification of a retinoic acid-sensitive period during primary axis formation in Xenopus laevis. , 1990, Genes & development.

[17]  M. Fisher,et al.  eFGF is required for activation of XmyoD expression in the myogenic cell lineage of Xenopus laevis. , 2002, Development.

[18]  M. Brand,et al.  Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. , 1998, Development.

[19]  N. Turner,et al.  Fibroblast growth factor signalling: from development to cancer , 2010, Nature Reviews Cancer.

[20]  William C. Smith,et al.  Revisions to the Xenopus gastrula fate map: Implications for mesoderm induction and patterning , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[21]  C. Stern Neural induction: old problem, new findings, yet more questions , 2005, Development.

[22]  J M Slack,et al.  Spatial response to fibroblast growth factor signalling in Xenopus embryos. , 1999, Development.

[23]  D. Rappolee,et al.  Expression and function of FGF-4 in peri-implantation development in mouse embryos. , 1994, Development.

[24]  Cornelis J. Weijer,et al.  PtdIns(3,4,5)P3-Dependent and -Independent Roles for PTEN in the Control of Cell Migration , 2007, Current Biology.

[25]  C. Hsieh,et al.  Germline Competent Embryonic Stem Cells Derived from Rat Blastocysts , 2008, Cell.

[26]  Cornelis J Weijer,et al.  Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8. , 2002, Developmental cell.

[27]  D. Lohnes,et al.  Retinoic acid regulates a subset of Cdx1 function in vivo , 2003, Development.

[28]  E. D. De Robertis,et al.  Integrating positional information at the level of Smad1/5/8. , 2008, Current opinion in genetics & development.

[29]  M. C. Jørgensen,et al.  Retinoic Acid Signaling Organizes Endodermal Organ Specification along the Entire Antero-Posterior Axis , 2009, PloS one.

[30]  J. Rossant,et al.  Opposite phenotypes of hypomorphic and Y766 phosphorylation site mutations reveal a function for Fgfr1 in anteroposterior patterning of mouse embryos. , 1998, Genes & development.

[31]  B. Doble,et al.  The ground state of embryonic stem cell self-renewal , 2008, Nature.

[32]  Russell B. Fletcher,et al.  The role of FGF signaling in the establishment and maintenance of mesodermal gene expression in Xenopus , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[33]  T. Jessell,et al.  An early requirement for FGF signalling in the acquisition of neural cell fate in the chick embryo , 2000, Current Biology.

[34]  Jeffrey M. Rosen,et al.  Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model , 2005, The Journal of cell biology.

[35]  N. Itoh The Fgf families in humans, mice, and zebrafish: their evolutional processes and roles in development, metabolism, and disease. , 2007, Biological & pharmaceutical bulletin.

[36]  V. Papaioannou,et al.  Requirement of FGF-4 for postimplantation mouse development , 1995, Science.

[37]  H. Müller,et al.  FGF8-like1 and FGF8-like2 Encode Putative Ligands of the FGF Receptor Htl and Are Required for Mesoderm Migration in the Drosophila Gastrula , 2004, Current Biology.

[38]  Vincent Bertrand,et al.  Neural Tissue in Ascidian Embryos Is Induced by FGF9/16/20, Acting via a Combination of Maternal GATA and Ets Transcription Factors , 2003, Cell.

[39]  Janet Rossant,et al.  The role of FGF/Erk signaling in pluripotent cells , 2010, Development.

[40]  Olivier Pourquié,et al.  fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo , 2004, Nature.

[41]  Ariel J. Levine,et al.  Proposal of a model of mammalian neural induction. , 2007, Developmental biology.

[42]  R. Harland,et al.  Ras-mediated FGF signaling is required for the formation of posterior but not anterior neural tissue in Xenopus laevis. , 2000, Developmental biology.

[43]  M. Kirschner,et al.  FGF signalling in the early specification of mesoderm in Xenopus. , 1993, Development.

[44]  D. Sredni,et al.  Opposite effects of FGF and BMP-4 on embryonic blood formation: roles of PV.1 and GATA-2. , 1999, Developmental biology.

[45]  C. Niehrs,et al.  A morphogen gradient of Wnt/beta-catenin signalling regulates anteroposterior neural patterning in Xenopus. , 2001, Development.

[46]  H. Hendriks,et al.  Retinoic acid causes an anteroposterior transformation in the developing central nervous system , 1989, Nature.

[47]  J. Rossant,et al.  Promotion of trophoblast stem cell proliferation by FGF4. , 1998, Science.

[48]  J. Slack,et al.  Regulation of Hox gene expression and posterior development by the Xenopus caudal homologue Xcad3 , 1998, The EMBO journal.

[49]  William C. Smith,et al.  The origins of primitive blood in Xenopus: implications for axial patterning. , 1999, Development.

[50]  N. Papalopulu,et al.  Temporal and spatial expression of FGF ligands and receptors during Xenopus development , 2009, Developmental dynamics : an official publication of the American Association of Anatomists.

[51]  C. Viebahn,et al.  FGF8 Acts as a Right Determinant during Establishment of the Left-Right Axis in the Rabbit , 2002, Current Biology.

[52]  E. D. De Robertis,et al.  Spemann’s organizer and the self-regulation of embryonic fields , 2009, Mechanisms of Development.

[53]  Mario dos Reis,et al.  Churchill, a Zinc Finger Transcriptional Activator, Regulates the Transition between Gastrulation and Neurulation , 2003, Cell.

[54]  C. Holt,et al.  Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does not affect mesoderm induction and patterning. , 2001, Genes & development.

[55]  Katsu Takahashi,et al.  Murine fibroblast growth factor receptor 1alpha isoforms mediate node regression and are essential for posterior mesoderm development. , 1999, Developmental biology.

[56]  T. Doniach Basic FGF as an inducer of anteroposterior neural pattern , 1995, Cell.

[57]  J. Rossant,et al.  Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts , 2005, Development.

[58]  J. Nichols,et al.  Validated germline-competent embryonic stem cell lines from nonobese diabetic mice , 2009, Nature Medicine.

[59]  R. Patient,et al.  Fibroblast growth factor controls the timing of Scl, Lmo2, and Runx1 expression during embryonic blood development. , 2008, Blood.

[60]  Janet Rossant,et al.  Cell and molecular regulation of the mouse blastocyst , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[61]  K. Kroll,et al.  Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation. , 1996, Development.

[62]  A. Wilkie Bad bones, absent smell, selfish testes: the pleiotropic consequences of human FGF receptor mutations. , 2005, Cytokine & growth factor reviews.

[63]  M. Fürthauer,et al.  Fgf signalling controls the dorsoventral patterning of the zebrafish embryo , 2004, Development.

[64]  Valerie Wilson,et al.  Stem cells, signals and vertebrate body axis extension , 2009, Development.

[65]  N. Hirokawa,et al.  FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left–right determination , 2005, Nature.

[66]  C. Kintner,et al.  Regulation of segmental patterning by retinoic acid signaling during Xenopus somitogenesis. , 2004, Developmental cell.

[67]  B. Shilo,et al.  Heartless, a Drosophila FGF receptor homolog, is essential for cell migration and establishment of several mesodermal lineages. , 1996, Genes & development.

[68]  E. D. De Robertis,et al.  Differential activation of Xenopus homeo box genes by mesoderm-inducing growth factors and retinoic acid. , 1990, Genes & development.

[69]  J. Gurdon,et al.  The heritage of experimental embryology: Hans Spemann and the organizer by Viktor Hamburger, Oxford University Press, 1988. £22.50/$29.95 (196 pages) ISBN 0 19505 110 6 , 1989, Trends in Neurosciences.

[70]  C. M. Sargent,et al.  Early posterior neural tissue is induced by FGF in the chick embryo. , 1998, Development.

[71]  A. Kuroiwa,et al.  Inhibition of BMP activity by the FGF signal promotes posterior neural development in zebrafish. , 2002, Developmental biology.

[72]  J M Slack,et al.  eFGF regulates Xbra expression during Xenopus gastrulation. , 1994, The EMBO journal.

[73]  R. Krumlauf,et al.  Initiating Hox gene expression: in the early chick neural tube differential sensitivity to FGF and RA signaling subdivides the HoxB genes in two distinct groups. , 2002, Development.

[74]  A. Kozubík,et al.  Molecular pathology of the fibroblast growth factor family , 2009, Human mutation.

[75]  M. Kirschner,et al.  Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in xenopus embryos , 1991, Cell.

[76]  N. Satoh,et al.  Early embryonic expression of FGF4/6/9 gene and its role in the induction of mesenchyme and notochord in Ciona savignyi embryos. , 2002, Development.

[77]  D. Ambrosetti,et al.  Mechanisms underlying differential responses to FGF signaling. , 2005, Cytokine & growth factor reviews.

[78]  P. Prinos,et al.  Retinoic Acid Regulation of Cdx1: an Indirect Mechanism for Retinoids and Vertebral Specification , 2000, Molecular and Cellular Biology.

[79]  J. Rossant,et al.  Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak. , 1997, Development.

[80]  C. MacArthur,et al.  Receptor Specificity of the Fibroblast Growth Factor Family* , 1996, The Journal of Biological Chemistry.

[81]  Russell B. Fletcher,et al.  FGF8 spliceforms mediate early mesoderm and posterior neural tissue formation in Xenopus , 2006, Development.

[82]  J. Nichols,et al.  Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo , 2009, Development.

[83]  R. Grainger,et al.  Expression of activated MAP kinase in Xenopus laevis embryos: evaluating the roles of FGF and other signaling pathways in early induction and patterning. , 2000, Developmental biology.

[84]  Y. Okamura,et al.  Basic fibroblast growth factor induction of neuronal ion channel expression in ascidian ectodermal blastomeres , 1998, The Journal of physiology.

[85]  S. Ota,et al.  The roles of the FGF signal in zebrafish embryos analyzed using constitutive activation and dominant-negative suppression of different FGF receptors , 2009, Mechanisms of Development.

[86]  D. Kimelman,et al.  Dorsal-ventral differences in Xcad-3 expression in response to FGF-mediated induction in Xenopus. , 1994, Developmental biology.

[87]  Shaun K Olsen,et al.  Receptor Specificity of the Fibroblast Growth Factor Family , 2006, Journal of Biological Chemistry.

[88]  N. Ueno,et al.  PKC delta is essential for Dishevelled function in a noncanonical Wnt pathway that regulates Xenopus convergent extension movements. , 2003, Genes & development.

[89]  H. Yost,et al.  Linkage of cardiac left-right asymmetry and dorsal-anterior development in Xenopus. , 1995, Development.

[90]  M. Kirschner,et al.  Synergistic induction of mesoderm by FGF and TGF-β and the identification of an mRNA coding for FGF in the early xenopus embryo , 1987, Cell.

[91]  R. Moon,et al.  Wnt and FGF pathways cooperatively pattern anteroposterior neural ectoderm in Xenopus , 1997, Mechanisms of Development.

[92]  J. Slack,et al.  FGF-8 is associated with anteroposterior patterning and limb regeneration in Xenopus. , 1997, Developmental biology.

[93]  J. Schlessinger Cell Signaling by Receptor Tyrosine Kinases , 2000, Cell.

[94]  C. Stern,et al.  Neural induction requires BMP inhibition only as a late step, and involves signals other than FGF and Wnt antagonists , 2004, Development.

[95]  A. Stathopoulos,et al.  FGF ligands in Drosophila have distinct activities required to support cell migration and differentiation , 2009, Development.

[96]  Scott E. Fraser,et al.  FGF receptor signalling is required to maintain neural progenitors during Hensen's node progression , 2001, Nature Cell Biology.

[97]  H. Okamoto,et al.  FGF signaling and the anterior neural induction in Xenopus. , 1999, Developmental biology.

[98]  M. Mohammadi,et al.  The FGF family: biology, pathophysiology and therapy , 2009, Nature Reviews Drug Discovery.

[99]  G. Martin,et al.  Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[100]  D. Kimelman Mesoderm induction: from caps to chips , 2006, Nature Reviews Genetics.

[101]  Y. Kawakami,et al.  Involvement of androgen-induced growth factor (FGF-8) gene in mouse embryogenesis and morphogenesis. , 1994, Biochemical and biophysical research communications.

[102]  Hiroshi Hamada,et al.  Establishment of vertebrate left–right asymmetry , 2002, Nature Reviews Genetics.

[103]  E. D. De Robertis,et al.  Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. , 2003, Genes & development.

[104]  J. Slack,et al.  Mesoderm induction in early Xenopus embryos by heparin-binding growth factors , 1987, Nature.

[105]  A. Streit,et al.  Cell communication with the neural plate is required for induction of neural markers by BMP inhibition: evidence for homeogenetic induction and implications for Xenopus animal cap and chick explant assays. , 2009, Developmental biology.

[106]  H. Yost,et al.  Role of notochord in specification of cardiac left-right orientation in zebrafish and Xenopus. , 1996, Developmental biology.

[107]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[108]  N. Papalopulu,et al.  FGF-8 stimulates neuronal differentiation through FGFR-4a and interferes with mesoderm induction in Xenopus embryos , 2000, Current Biology.

[109]  M. Fürthauer,et al.  A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula. , 1997, Development.

[110]  E. Jabs,et al.  The pleiotropic effects of fibroblast growth factor receptors in mammalian development. , 2000, Cell structure and function.

[111]  G. Martin,et al.  FGF-4 and BMP-2 have opposite effects on limb growth , 1993, Nature.

[112]  G. Kumano,et al.  Boundaries and functional domains in the animal/vegetal axis of Xenopus gastrula mesoderm. , 2001, Developmental biology.

[113]  A. Deconinck,et al.  FGF4 regulates blood and muscle specification in Xenopus laevis , 2007, Biology of the cell.

[114]  H. Isaacs,et al.  FGF signal transduction and the regulation of Cdx gene expression. , 2006, Developmental biology.

[115]  P. Tam,et al.  Exogenous FGF-4 can suppress anterior development in the mouse embryo during neurulation and early organogenesis. , 2000, Developmental biology.

[116]  V. García-Martínez,et al.  Targeted over-expression of FGF in chick embryos induces formation of ectopic neural cells. , 1997, The International journal of developmental biology.

[117]  J. Rossant Stem Cells and Early Lineage Development , 2008, Cell.

[118]  Jihwan Song,et al.  Multiple points of interaction between retinoic acid and FGF signaling during embryonic axis formation , 2004, Development.

[119]  Tony Pawson,et al.  Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. , 2006, Developmental cell.

[120]  C. Hudson,et al.  FGF8/17/18 functions together with FGF9/16/20 during formation of the notochord in Ciona embryos. , 2007, Developmental biology.

[121]  Sheng Ding,et al.  Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. , 2009, Cell stem cell.

[122]  E. D. De Robertis,et al.  Dorsal-ventral patterning and neural induction in Xenopus embryos. , 2004, Annual review of cell and developmental biology.

[123]  A. Streit,et al.  Initiation of neural induction by FGF signalling before gastrulation , 2000, Nature.

[124]  P. Nieuwkoop Activation and organization of the central nervous system in amphibians. Part II. Differentiation and organization , 1952 .

[125]  D. Gospodarowicz,et al.  Mitogenic effect of fibroblast growth factor on early passage cultures of human and murine fibroblasts , 1975, The Journal of cell biology.

[126]  G. Martin,et al.  Genetic evidence that FGFs have an instructive role in limb proximal–distal patterning , 2008, Nature.

[127]  Hajime Yamauchi,et al.  Fgf4 is required for left-right patterning of visceral organs in zebrafish. , 2009, Developmental biology.

[128]  H. Okamoto,et al.  Integration of multiple signal transducing pathways on Fgf response elements of the Xenopus caudal homologue Xcad3 , 2003, Development.

[129]  G. Martin,et al.  Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo. , 1999, Genes & development.

[130]  William C. Smith,et al.  FGF signaling restricts the primary blood islands to ventral mesoderm. , 2000, Developmental biology.

[131]  Alexander F Schier,et al.  Molecular genetics of axis formation in zebrafish. , 2005, Annual review of genetics.

[132]  J. Slack,et al.  Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification. , 1992, Development.

[133]  Austin G Smith,et al.  Capture of Authentic Embryonic Stem Cells from Rat Blastocysts , 2008, Cell.

[134]  A. Bradley,et al.  Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines , 1984, Nature.

[135]  F. Rentzsch,et al.  Fgf signaling induces posterior neuroectoderm independently of Bmp signaling inhibition , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[136]  Robert Geisler,et al.  Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation , 2000, Nature.

[137]  Janet Rossant,et al.  FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst , 2010, Development.

[138]  G. Martin,et al.  An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination , 1998, Nature Genetics.

[139]  K. Storey,et al.  Opposing FGF and retinoid pathways: a signalling switch that controls differentiation and patterning onset in the extending vertebrate body axis , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[140]  P. Nieuwkoop,et al.  Activation and organization of the central nervous system in amphibians. Part III. Synthesis of a new working hypothesis , 1952 .

[141]  Emily Gale,et al.  Opposing FGF and Retinoid Pathways Control Ventral Neural Pattern, Neuronal Differentiation, and Segmentation during Body Axis Extension , 2003, Neuron.

[142]  R. Ho,et al.  Zebrafish SPI-1 (PU.1) marks a site of myeloid development independent of primitive erythropoiesis: implications for axial patterning. , 2002, Developmental biology.

[143]  H. Müller,et al.  Differential and overlapping functions of two closely related Drosophila FGF8-like growth factors in mesoderm development , 2009, Development.

[144]  I. Mason,et al.  Expression of Fgf4 during early development of the chick embryo , 1999, Mechanisms of Development.

[145]  J. Smith,et al.  Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. , 2000, Development.

[146]  G. Duester,et al.  Effect of retinoic acid signaling on Wnt/beta-catenin and FGF signaling during body axis extension. , 2009, Gene expression patterns : GEP.

[147]  Austin G Smith,et al.  FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment , 2007, Development.

[148]  Andrea Vortkamp,et al.  Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. , 2002, Developmental cell.

[149]  G. Martin,et al.  Differences in left-right axis pathways in mouse and chick: functions of FGF8 and SHH. , 1999, Science.

[150]  N. Pilon,et al.  Cdx4 is a direct target of the canonical Wnt pathway. , 2006, Developmental biology.

[151]  J. Schlessinger,et al.  Cell Signaling by Receptor Tyrosine Kinases , 2000, Cell.

[152]  D. McClay,et al.  FGF signals guide migration of mesenchymal cells, control skeletal morphogenesis and regulate gastrulation during sea urchin development , 2007 .

[153]  Sung-Kook Hong,et al.  FGF-dependent left–right asymmetry patterning in zebrafish is mediated by Ier2 and Fibp1 , 2009, Proceedings of the National Academy of Sciences.

[154]  S. Komune,et al.  Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis , 2009, Oncogene.

[155]  P. Dollé,et al.  Early mouse caudal development relies on crosstalk between retinoic acid, Shh and Fgf signalling pathways , 2009, Development.

[156]  D. Melton,et al.  Early mouse endoderm is patterned by soluble factors from adjacent germ layers. , 2000, Development.

[157]  Stephen W. Wilson,et al.  Combinatorial Fgf and Bmp signalling patterns the gastrula ectoderm into prospective neural and epidermal domains , 2004, Development.

[158]  N. Itoh,et al.  Functional evolutionary history of the mouse Fgf gene family , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[159]  Christof Niehrs,et al.  Fibroblast growth factor signaling during early vertebrate development. , 2005, Endocrine reviews.

[160]  C. Kimmel,et al.  Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development , 2003, Development.

[161]  C. Weaver,et al.  Move it or lose it: axis specification in Xenopus , 2004, Development.

[162]  H. Yost,et al.  FGF signalling during embryo development regulates cilia length in diverse epithelia , 2010, Nature.

[163]  J. Rossant,et al.  fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. , 1994, Genes & development.

[164]  Marios P. Stavridis,et al.  A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification , 2007, Development.

[165]  G. Martin,et al.  The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. , 1995, Development.

[166]  J. Sivak,et al.  FGF signal interpretation is directed by Sprouty and Spred proteins during mesoderm formation. , 2005, Developmental cell.

[167]  J. Slack The heritage of experimental embryology: Hans Spemann and the organizer , 1989, Medical History.

[168]  C. Tabin,et al.  Left–right development: Conserved function for embryonic nodal cilia , 2002, Nature.

[169]  Stephen W. Wilson,et al.  Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm. , 2002, Development.

[170]  R. Evans,et al.  An essential role for retinoid signaling in anteroposterior neural patterning. , 1997, Development.

[171]  D. Shi,et al.  A truncated FGF receptor blocks neural induction by endogenous Xenopus inducers. , 1996, Development.

[172]  J. Heath,et al.  Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[173]  L. Faas,et al.  Characterisation of the Fibroblast Growth Factor Dependent Transcriptome in Early Development , 2009, PloS one.

[174]  A. McMahon,et al.  Wnt-3a regulates somite and tailbud formation in the mouse embryo. , 1994, Genes & development.

[175]  S. Sokol,et al.  FGF is required for posterior neural patterning but not for neural induction. , 1999, Developmental biology.

[176]  K. Storey,et al.  Wnt signals provide a timing mechanism for the FGF-retinoid differentiation switch during vertebrate body axis extension , 2007, Development.

[177]  R. Harland,et al.  Fibroblast growth factor is a direct neural inducer, which combined with noggin generates anterior-posterior neural pattern. , 1995, Development.

[178]  J. Slack,et al.  eFGF is expressed in the dorsal midline of Xenopus laevis. , 1995, The International journal of developmental biology.

[179]  J. Slack,et al.  eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus. , 1996, Development.

[180]  M. Sheets,et al.  Primitive and definitive blood share a common origin in Xenopus: a comparison of lineage techniques used to construct fate maps. , 2002, Developmental biology.

[181]  R. Moon,et al.  Specification of the anteroposterior neural axis through synergistic interaction of the Wnt signaling cascade with noggin and follistatin. , 1995, Developmental biology.

[182]  Shawn C. Little,et al.  Extracellular modulation of BMP activity in patterning the dorsoventral axis. , 2006, Birth defects research. Part C, Embryo today : reviews.

[183]  L. Saxén,et al.  The two-gradient hypothesis in primary induction. The combined effect of two types of inductors mixed in different ratios. , 1961, Journal of embryology and experimental morphology.

[184]  M. Kessel,et al.  FGF8 functions in the specification of the right body side of the chick , 1999, Current Biology.

[185]  Marios P. Stavridis,et al.  Development and Stem Cells Research Article , 2022 .

[186]  M. Khokha,et al.  BMP antagonists and FGF signaling contribute to different domains of the neural plate in Xenopus. , 2010, Developmental biology.

[187]  J. Rossant,et al.  Spatial and temporal patterns of ERK signaling during mouse embryogenesis , 2003, Development.

[188]  Christian Wehrle,et al.  Wnt3a plays a major role in the segmentation clock controlling somitogenesis. , 2003, Developmental cell.