Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo

Genetic studies have identified the key signalling pathways and developmentally regulated transcription factors that govern cell lineage allocation and axis patterning in the early mammalian embryo. Recent advances have uncovered details of the molecular circuits that tightly control cell growth and differentiation in the mammalian embryo from the blastocyst stage, through the establishment of initial anterior–posterior polarity, to gastrulation, when the germ cells are set aside and the three primary germ layers are specified. Relevant studies in lower vertebrates indicate the conservation and divergence of regulatory mechanisms for cell lineage allocation and axis patterning.

[1]  R. Behringer,et al.  Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. , 2002, Developmental cell.

[2]  P. Khoo,et al.  Dkk1 and Wnt3 interact to control head morphogenesis in the mouse , 2008, Development.

[3]  P. Wassarman,et al.  Differentiation of embryonic stem cells , 2003 .

[4]  Mark M. Davis,et al.  The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse , 2005, Development.

[5]  K. Anderson,et al.  Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching , 2006, Development.

[6]  D. Norris,et al.  Cell fate decisions within the mouse organizer are governed by graded Nodal signals. , 2003, Genes & development.

[7]  M. Surani,et al.  Germ Cell Specification in Mice , 2007, Science.

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

[9]  P. Pfeffer,et al.  Loss of the extraembryonic ectoderm in Elf5 mutants leads to defects in embryonic patterning , 2005, Development.

[10]  E. Bikoff,et al.  Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo , 2004, Development.

[11]  Natasa Przulj,et al.  High-Throughput Mapping of a Dynamic Signaling Network in Mammalian Cells , 2005, Science.

[12]  M. Trotter,et al.  Derivation of pluripotent epiblast stem cells from mammalian embryos , 2007, Nature.

[13]  J. Rossant,et al.  Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells. , 2008, Cell stem cell.

[14]  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.

[15]  F. Conlon,et al.  A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. , 1994, Development.

[16]  N. Daigle,et al.  A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. , 1996, Development.

[17]  Heiko Lickert,et al.  Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm. , 2002, Developmental cell.

[18]  D. Kane,et al.  One-eyed pinhead regulates cell motility independent of Squint/Cyclops signaling. , 2003, Developmental biology.

[19]  Li Chai,et al.  Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1 , 2006, Nature Cell Biology.

[20]  A. G. Herreros,et al.  The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells , 2000, Nature Cell Biology.

[21]  Allan Bradley,et al.  Requirement for Wnt3 in vertebrate axis formation , 1999, Nature Genetics.

[22]  J. Rossant,et al.  Crucial roles of Foxa2 in mouse anterior–posterior axis polarization via regulation of anterior visceral endoderm-specific genes , 2007, Proceedings of the National Academy of Sciences.

[23]  R. Pedersen,et al.  Clonal analysis of cell fate during gastrulation and early neurulation in the mouse. , 1992, Ciba Foundation symposium.

[24]  Janet Rossant,et al.  Cdx 2 acts downstream of cell polarization to cell-autonomously promote trophectoderm fate in the early mouse embryo , 2008 .

[25]  Yoshiakira Kanai,et al.  Depletion of definitive gut endoderm in Sox17-null mutant mice. , 2002, Development.

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

[27]  Francisco Portillo,et al.  The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression , 2000, Nature Cell Biology.

[28]  R. Krumlauf,et al.  Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm. , 1997, Development.

[29]  M. Shen Nodal signaling: developmental roles and regulation , 2007, Development.

[30]  R. Beddington,et al.  Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo , 1996, Current Biology.

[31]  A. Fukui,et al.  SDF-1α regulates mesendodermal cell migration during frog gastrulation , 2007 .

[32]  Takashi Hiiragi,et al.  Stochastic patterning in the mouse pre-implantation embryo , 2007, Development.

[33]  K. Lawson Fate mapping the mouse embryo. , 1999, The International journal of developmental biology.

[34]  B. Hogan,et al.  Bmp4 is required for the generation of primordial germ cells in the mouse embryo. , 1999, Genes & development.

[35]  Cindy C. Lu,et al.  Multiple roles for Nodal in the epiblast of the mouse embryo in the establishment of anterior-posterior patterning. , 2004, Developmental biology.

[36]  A. Camus,et al.  Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo. , 2006, Developmental biology.

[37]  Y. Saijoh,et al.  Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2. , 2000, Molecular cell.

[38]  C. Mummery,et al.  BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. , 2004, Genes & development.

[39]  A. Kuroiwa,et al.  Sdf1/Cxcr4 signaling controls the dorsal migration of endodermal cells during zebrafish gastrulation , 2008, Development.

[40]  Ryan M. Anderson,et al.  The organizer factors Chordin and Noggin are required for mouse forebrain development , 2000, Nature.

[41]  H. Hamada,et al.  Origin of body axes in the mouse embryo. , 2007 .

[42]  D. Page,et al.  Dppa 3 / Pgc 7 / stellais a maternal factor and is not required for germ cell specification in mice Citation , 2004 .

[43]  M. Surani,et al.  A molecular programme for the specification of germ cell fate in mice , 2002, Nature.

[44]  E. Bikoff,et al.  Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. , 2006, Developmental biology.

[45]  U. Hofmann,et al.  Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse , 2008, Development.

[46]  P. Tam,et al.  IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion. , 2005, Developmental cell.

[47]  R. Gardner,et al.  Complete dissipation of coherent clonal growth occurs before gastrulation in mouse epiblast. , 1998, Development.

[48]  J. Rossant,et al.  Ets2 is necessary in trophoblast for normal embryonic anteroposterior axis development , 2006, Development.

[49]  B. Hogan,et al.  Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. , 1995, Genes & development.

[50]  Scott E Fraser,et al.  Convergent extension: the molecular control of polarized cell movement during embryonic development. , 2002, Developmental cell.

[51]  Janet Rossant,et al.  Interaction between Oct3/4 and Cdx2 Determines Trophectoderm Differentiation , 2005, Cell.

[52]  R. Beddington,et al.  Nodal signalling in the epiblast patterns the early mouse embryo , 2001, Nature.

[53]  K. Anderson,et al.  p38 and a p38-Interacting Protein Are Critical for Downregulation of E-Cadherin during Mouse Gastrulation , 2006, Cell.

[54]  Wei Hsu,et al.  The Mouse Fused Locus Encodes Axin, an Inhibitor of the Wnt Signaling Pathway That Regulates Embryonic Axis Formation , 1997, Cell.

[55]  K. Kurimoto,et al.  Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. , 2008, Genes & development.

[56]  Robert A. Weinberg,et al.  Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. , 2008, Developmental cell.

[57]  E. Robertis,et al.  Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal , 2007, Cell.

[58]  R. Schwartz,et al.  Sox17 is essential for the specification of cardiac mesoderm in embryonic stem cells , 2007, Proceedings of the National Academy of Sciences.

[59]  Liming Yang,et al.  Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. , 2002, Immunity.

[60]  Ken W. Y. Cho,et al.  Ventral closure, headfold fusion and definitive endoderm migration defects in mouse embryos lacking the fibronectin leucine-rich transmembrane protein FLRT3. , 2008, Developmental biology.

[61]  J. Walsh,et al.  Arkadia enhances nodal-related signalling to induce mesendoderm , 2001, Nature.

[62]  J. Rossant,et al.  Disruption of early proximodistal patterning and AVE formation in Apc mutants , 2006, Development.

[63]  Y. Saka,et al.  A mechanism for the sharp transition of morphogen gradient interpretation in Xenopus , 2007, BMC Developmental Biology.

[64]  Y. Mishina,et al.  BMP signalling inhibits premature neural differentiation in the mouse embryo , 2007, Development.

[65]  Michael Kyba,et al.  Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. , 2008, Cell stem cell.

[66]  Dorian C. Anderson,et al.  Differential requirements for Smad4 in TGFβ-dependent patterning of the early mouse embryo , 2004, Development.

[67]  Andrew P. McMahon,et al.  Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity , 1993, Cell.

[68]  D. Constam,et al.  Nodal specifies embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning , 2006, Development.

[69]  Dorian C. Anderson,et al.  Summary Differential requirements for Smad 4 in TGF β-dependent patterning of the early mouse embryo , 2022 .

[70]  Gordon Keller,et al.  Differentiation of Embryonic Stem Cells to Clinically Relevant Populations: Lessons from Embryonic Development , 2008, Cell.

[71]  Janet Rossant,et al.  Dynamic expression of Lrp2 pathway members reveals progressive epithelial differentiation of primitive endoderm in mouse blastocyst. , 2008, Developmental biology.

[72]  Y. Saga,et al.  Summary MesP 1 and MesP 2 are essential for the development of cardiac mesoderm , 2000 .

[73]  T. Speed,et al.  Inner cell allocation in the mouse morula: the role of oriented division during fourth cleavage. , 1990, Developmental Biology.

[74]  W. Skarnes,et al.  The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice , 2004, Development.

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

[76]  S. Aparício,et al.  Eomesodermin is required for mouse trophoblast development and mesoderm formation , 2000, Nature.

[77]  M. Nussenzweig,et al.  Blimp1 Defines a Progenitor Population that Governs Cellular Input to the Sebaceous Gland , 2006, Cell.

[78]  A. Wynshaw-Boris,et al.  Cripto is required for correct orientation of the anterior–posterior axis in the mouse embryo , 1998, Nature.

[79]  Jeffrey L. Wrana,et al.  A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation , 1999, Nature.

[80]  Bernhard Schmierer,et al.  TGFβ–SMAD signal transduction: molecular specificity and functional flexibility , 2007, Nature Reviews Molecular Cell Biology.

[81]  E. Robertson,et al.  Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation. , 2001, Development.

[82]  P. Donahoe,et al.  The type I activin receptor ActRIB is required for egg cylinder organization and gastrulation in the mouse. , 1998, Genes & development.

[83]  P. Hoodless,et al.  Formation of the definitive endoderm is a Smad2-dependent process , 2000 .

[84]  M. Capecchi,et al.  Inactivation of the FGF-4 gene in embryonic stem cells alters the growth and/or the survival of their early differentiated progeny. , 1997, Developmental biology.

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

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

[87]  E. Carver,et al.  The Mouse Snail Gene Encodes a Key Regulator of the Epithelial-Mesenchymal Transition , 2001, Molecular and Cellular Biology.

[88]  L. Wolpert,et al.  The amniote primitive streak is defined by epithelial cell intercalation before gastrulation , 2007, Nature.

[89]  Tony Pawson,et al.  Mammalian Grb2 Regulates Multiple Steps in Embryonic Development and Malignant Transformation , 1998, Cell.

[90]  R. Behringer,et al.  HNF3beta and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo. , 1999, Development.

[91]  J. Rossant,et al.  FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse. , 2001, Genes & development.

[92]  R. Braun,et al.  Pathway to Totipotency: Lessons from Germ Cells , 2006, Cell.

[93]  M. Saitou,et al.  Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences. , 2010, Reproduction.

[94]  D. Constam,et al.  Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[95]  R. Beddington,et al.  Active cell migration drives the unilateral movements of the anterior visceral endoderm , 2004, Development.

[96]  R. Behringer,et al.  Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. , 1995, Genes & development.

[97]  Ken W. Y. Cho,et al.  TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis. , 2007, Genes & development.

[98]  J. Brennan,et al.  From fertilization to gastrulation: axis formation in the mouse embryo. , 2001, Current opinion in genetics & development.

[99]  R. Beddington,et al.  Axis Development and Early Asymmetry in Mammals , 1999, Cell.

[100]  Gordon Keller,et al.  Development of definitive endoderm from embryonic stem cells in culture , 2004, Development.

[101]  M. DePamphilis,et al.  Transcription factor TEAD4 specifies the trophectoderm lineage at the beginning of mammalian development , 2007, Development.

[102]  Janet Rossant,et al.  Cdx2 acts downstream of cell polarization to cell-autonomously promote trophectoderm fate in the early mouse embryo. , 2008, Developmental biology.

[103]  M. Azim Surani,et al.  Blimp1 is a critical determinant of the germ cell lineage in mice , 2005, Nature.

[104]  J. Rossant,et al.  Live imaging and genetic analysis of mouse notochord formation reveals regional morphogenetic mechanisms. , 2007, Developmental cell.

[105]  R. McKay,et al.  New cell lines from mouse epiblast share defining features with human embryonic stem cells , 2007, Nature.

[106]  K. Kurimoto,et al.  Gene Expression Dynamics During Germline Specification in Mice Identified by Quantitative Single-Cell Gene Expression Profiling1 , 2006, Biology of reproduction.

[107]  D. Constam,et al.  Evolution of the mechanisms and molecular control of endoderm formation , 2007, Mechanisms of Development.

[108]  M. Surani,et al.  Normal Germ Line Establishment in Mice Carrying a Deletion of the Ifitm/Fragilis Gene Family Cluster , 2008, Molecular and Cellular Biology.

[109]  J. I. Izpisúa Belmonte,et al.  Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. , 2001, Developmental cell.

[110]  K. Calame,et al.  Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1 , 2007, Proceedings of the National Academy of Sciences.

[111]  M. Murakami,et al.  The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells , 2003, Cell.

[112]  D. Constam,et al.  The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4. , 2006, Developmental cell.

[113]  Carmen Birchmeier,et al.  Requirement for β-Catenin in Anterior-Posterior Axis Formation in Mice , 2000, The Journal of cell biology.

[114]  Y. Matsui,et al.  Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm. , 2005, Developmental cell.

[115]  Elizabeth J. Robertson,et al.  Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice , 2007, Development.

[116]  M. Azim Surani,et al.  Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells , 2006, Nature Cell Biology.

[117]  H. Woodland,et al.  Regulation of the Xenopus Xsox 17 α 1 promoter by co-operating VegT and Sox 17 sites , 2007 .

[118]  R. Beddington,et al.  Induction and migration of the anterior visceral endoderm is regulated by the extra-embryonic ectoderm , 2005, Development.

[119]  M. Kuehn,et al.  Genetic dissection of nodal function in patterning the mouse embryo. , 2001, Development.

[120]  Yue Zhang,et al.  Regulation of the Polarity Protein Par6 by TGFß Receptors Controls Epithelial Cell Plasticity , 2005, Science.

[121]  M. Surani,et al.  Proximal visceral endoderm and extraembryonic ectoderm regulate the formation of primordial germ cell precursors , 2007, BMC Developmental Biology.

[122]  R. Pedersen,et al.  Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. , 1991, Development.

[123]  Yongmei Liu,et al.  Genome-wide identification of Smad/Foxh1 targets reveals a role for Foxh1 in retinoic acid regulation and forebrain development. , 2008, Developmental cell.

[124]  藤倉 純二 Differentiation of embryonic stem cells is induced by GATA factors , 2003 .

[125]  A. Hadjantonakis,et al.  The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. , 2008, Developmental cell.

[126]  Y. Saijoh,et al.  The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse. , 2001, Genes & development.

[127]  Carmen Birchmeier,et al.  Requirement for beta-catenin in anterior-posterior axis formation in mice. , 2000 .

[128]  Y. Saga,et al.  MesP1 and MesP2 are essential for the development of cardiac mesoderm. , 2000, Development.

[129]  J. Rossant,et al.  The transcription factor HNF3beta is required in visceral endoderm for normal primitive streak morphogenesis. , 1998, Development.

[130]  R. Arkell,et al.  Induction of the mammalian node requires Arkadia function in the extraembryonic lineages , 2001, Nature.

[131]  K. Calame,et al.  Regulation and functions of Blimp-1 in T and B lymphocytes. , 2008, Annual review of immunology.

[132]  J. Nichols,et al.  Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells , 2003, Cell.

[133]  K. Kurimoto,et al.  Critical function of Prdm14 for the establishment of the germ cell lineage in mice , 2008, Nature Genetics.

[134]  Y. Saijoh,et al.  Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo , 2004, Nature.

[135]  多田 真輔 Characterization of mesendoderm : a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture , 2006 .

[136]  P. Hoodless,et al.  Smad2 Signaling in Extraembryonic Tissues Determines Anterior-Posterior Polarity of the Early Mouse Embryo , 1998, Cell.

[137]  R. Klein,et al.  Immune and nervous system CXCL12 and CXCR4: parallel roles in patterning and plasticity. , 2004, Trends in immunology.

[138]  P. Brûlet,et al.  Otx2 is required for visceral endoderm movement and for the restriction of posterior signals in the epiblast of the mouse embryo. , 2001, Development.

[139]  Wei Wang,et al.  Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs. , 2008, Cell stem cell.

[140]  J. Brennan,et al.  The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo. , 2002, Development.

[141]  J. Miyazaki,et al.  MesP1 is expressed in the heart precursor cells and required for the formation of a single heart tube. , 1999, Development.

[142]  D. Norris,et al.  Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements. , 1999, Genes & development.

[143]  M. Rugge,et al.  Germ-Layer Specification and Control of Cell Growth by Ectodermin, a Smad4 Ubiquitin Ligase , 2005, Cell.

[144]  H. Woodland,et al.  Regulation of the Xenopus Xsox17α1 promoter by co-operating VegT and Sox17 sites , 2007, Developmental biology.

[145]  Y. Matsui,et al.  Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. , 2005, Developmental biology.

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

[147]  J. Massagué,et al.  TGFβ in Cancer , 2008, Cell.

[148]  Xiaozhong Wang,et al.  Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK). , 2001, Development.

[149]  J. Rossant,et al.  FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. , 2001, Developmental cell.

[150]  Hans Clevers,et al.  Wnt/β-Catenin Signaling in Development and Disease , 2006, Cell.

[151]  Roles and regulation , 2006, Veterinary Record.