Roles of nodal‐lefty regulatory loops in embryonic patterning of vertebrates

Nodal is a signalling molecule that belongs to the transforming growth factor–β superfamily of proteins, and Lefty proteins are antagonists of Nodal signalling. The nodal and lefty genes form positive and negative regulatory loops that resemble the reaction‐diffusion system. As a pair, these genes control various events of vertebrate embryonic patterning, including left‐right specification and mesoderm formation. In this review, we will focus on recent studies that have addressed the roles of nodal and lefty in mouse development.

[1]  A. Schier,et al.  Nodal signalling in vertebrate development , 2000, Nature.

[2]  Xin Chen,et al.  A transcriptional partner for MAD proteins in TGF-β signalling , 1996, Nature.

[3]  M. Khokha,et al.  Insertional mutation of a gene involved in growth regulation of the early mouse embryo , 1992, Developmental dynamics : an official publication of the American Association of Anatomists.

[4]  W. Talbot,et al.  Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. , 1999, Genes & development.

[5]  M. Gates,et al.  Zebrafish organizer development and germ-layer formation require nodal-related signals , 1998, Nature.

[6]  J. Collignon,et al.  Relationship between asymmetric nodal expression and the direction of embryonic turning , 1996, Nature.

[7]  H. Hamada,et al.  Asymmetric expression of antivin/lefty1 in the early chick embryo , 2000, Mechanisms of Development.

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

[9]  J. Creemers,et al.  Lefty Proteins Exhibit Unique Processing and Activate the MAPK Pathway* , 2001, The Journal of Biological Chemistry.

[10]  C. Tabin,et al.  Antagonistic Signaling by Caronte, a Novel Cerberus-Related Gene, Establishes Left–Right Asymmetric Gene Expression , 1999, Cell.

[11]  Y. Saijoh,et al.  Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer. , 1999, Genes & development.

[12]  M. Whitman,et al.  Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. , 2001, Molecular cell.

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

[14]  S. Aizawa,et al.  Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast. , 2001, Developmental biology.

[15]  S. Germain,et al.  Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif. , 2000, Genes & development.

[16]  J. Collignon,et al.  nodal expression in the primitive endoderm is required for specification of the anterior axis during mouse gastrulation. , 1997, Development.

[17]  Naoto Ueno,et al.  Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer , 2000, Nature.

[18]  Y. Saijoh,et al.  lefty-1 Is Required for Left-Right Determination as a Regulator of lefty-2 and nodal , 1998, Cell.

[19]  Y. Saijoh,et al.  Left–right asymmetric expression of the TGFβ-family member lefty in mouse embryos , 1996, Nature.

[20]  D. Supp,et al.  Conserved left–right asymmetry of nodal expression and alterations in murine situs inversus , 1996, Nature.

[21]  A. Schier.  Nodal signaling in vertebrate development. , 2003, Annual review of cell and developmental biology.

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

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

[24]  Y. Saijoh,et al.  Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2. , 2001, Molecular cell.

[25]  C. Tabin,et al.  Mechanisms of Left–Right Determination in Vertebrates , 2000, Cell.

[26]  Linda Lowe,et al.  Nodal is a novel TGF-β-like gene expressed in the mouse node during gastrulation , 1993, Nature.

[27]  S. Aizawa,et al.  Visceral endoderm mediates forebrain development by suppressing posteriorizing signals. , 2000, Developmental biology.

[28]  M. Whitman.  Smads and early developmental signaling by the TGFbeta superfamily. , 1998, Genes & development.

[29]  R. Beddington,et al.  Anterior patterning in mouse. , 1998, Trends in genetics : TIG.

[30]  Y. Saijoh,et al.  Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2. , 1999, Genes & development.

[31]  E. Stanley,et al.  Murine cerberus homologue mCer-1: a candidate anterior patterning molecule. , 1998, Developmental biology.

[32]  Nihon Hassei Seibutsu Gakkai,et al.  Genes to cells , 1996 .

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

[34]  R. Kucherlapati,et al.  Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[35]  E. Li,et al.  Smad2 role in mesoderm formation, left–right patterning and craniofacial development , 1998, Nature.

[36]  A. Celeste,et al.  Nodal Signaling Uses Activin and Transforming Growth Factor-β Receptor-regulated Smads* , 2001, The Journal of Biological Chemistry.

[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]  S. Kuhara,et al.  Two closely‐related left‐right asymmetrically expressed genes, lefty‐1 and lefty‐2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos , 1997, Genes to cells : devoted to molecular & cellular mechanisms.

[39]  S. P. Oh,et al.  The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse. , 1997, Genes & development.

[40]  J. Smith,et al.  Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation. , 1995, Development.

[41]  H. Yost,et al.  Regulation of midline development by antagonism of lefty and nodal signaling. , 1999, Development.

[42]  한평림.  A Transcriptional Partner for MAD Proteins in TGF - b Signalling , 1996 .

[43]  Y. Saijoh,et al.  Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes , 2000, Genes to cells : devoted to molecular & cellular mechanisms.

[44]  W. Talbot,et al.  Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation. , 1999, Molecular cell.

[45]  Smads and early developmental signaling by the TGFbeta superfamily. , 1998, Genes & development.

[46]  S. P. Oh,et al.  The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice. , 1999, Developmental biology.

[47]  S. Kondo,et al.  A reaction–diffusion wave on the skin of the marine angelfish Pomacanthus , 1995, Nature.

[48]  Y. Saijoh,et al.  Activin/nodal responsiveness and asymmetric expression of a Xenopus nodal-related gene converge on a FAST-regulated module in intron 1. , 2000, Development.

[49]  M. Sekiguchi.  Genes to cells: edited by Jun-ichi Tomizawa, Blackwell Science Ltd. Institutional: £218.00 (Europe), £242.00 (Rest of World), US$382.00 (USA and Canada). Individual: £65.00 (Europe), £72.00 (Rest of World), US$114.00 (USA and Canada) ISSN 1356 9597 , 1997 .

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

[51]  C. Wright,et al.  The lefty-related factor Xatv acts as a feedback inhibitor of nodal signaling in mesoderm induction and L-R axis development in xenopus. , 2000, Development.

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

[53]  T. Bouwmeester,et al.  Cerberus-like is a secreted factor with neuralizing activity expressed in the anterior primitive endoderm of the mouse gastrula , 1997, Mechanisms of Development.

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

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

[56]  B. Thisse,et al.  Antivin, a novel and divergent member of the TGFbeta superfamily, negatively regulates mesoderm induction. , 1999, Development.

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

[58]  J. Miyazaki,et al.  Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2. , 2001, Developmental cell.

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

[60]  I. Kirsch,et al.  The SIL gene is required for mouse embryonic axial development and left–right specification , 1999, Nature.

[61]  I B Dawid,et al.  Nodal induces ectopic goosecoid and lim1 expression and axis duplication in zebrafish. , 1995, Development.

[62]  R. Beddington,et al.  Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors. , 1998, Development.

[63]  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.

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

[65]  C. R. Esteban,et al.  The novel Cer-like protein Caronte mediates the establishment of embryonic left–right asymmetry , 1999, Nature.