NODAL and SHH dose-dependent double inhibition promotes an HPE-like phenotype in chick embryos

(HPE) is the most common congenital forebrain defect in humans. It results from failed or incomplete forebrain cleavage between days 18 and 28 of gestation (Dubourg et al., 2007; Marcorelles and Laquerriere, 2010). The clinical presentation of HPE is remarkably variable, and the severity of the defects observed is evenly distributed along the HPE spectrum. The etiology is very complex and heterogeneous, involving chromosomal anomalies, multiple malformation syndromes and environmental factors. Fourteen genes are known to be involved in non-syndromic human HPE and CDON), but they explain only 30% of HPE cases (Mercier et al., 2011). All mutations are found in the heterozygous state in HPE patients, and most are loss-of-function mutations The correlation between the HPE phenotype and genotype is poor, and both sporadic cases and pedigrees display the extensive HPE phenotype variability. This suggests that heterozygous mutations of HPE genes might be insufficient to produce severe anomalies, and that HPE is the consequence of a complex interplay of

[1]  Adam R. Navis.  A series of normal stages in the development of the chick embryo. 1951. , 2012, Developmental dynamics : an official publication of the American Association of Anatomists.

[2]  M. Muenke,et al.  Utilizing prospective sequence analysis of SHH, ZIC2, SIX3 and TGIF in holoprosencephaly probands to describe the parameters limiting the observed frequency of mutant gene×gene interactions. , 2012, Molecular genetics and metabolism.

[3]  S. Gaines,et al.  The Mouse , 2011 .

[4]  I. Gicquel,et al.  New findings for phenotype–genotype correlations in a large European series of holoprosencephaly cases , 2011, Journal of Medical Genetics.

[5]  M. Muenke,et al.  Mutations in CDON, encoding a hedgehog receptor, result in holoprosencephaly and defective interactions with other hedgehog receptors. , 2011, American journal of human genetics.

[6]  T. Bohan,et al.  NOTCH, a new signaling pathway implicated in holoprosencephaly. , 2011, Human molecular genetics.

[7]  Wei Zhang,et al.  Boc modifies the holoprosencephaly spectrum of Cdo mutant mice , 2010, Disease Models & Mechanisms.

[8]  Nathan M. Young,et al.  Quantitative analyses link modulation of sonic hedgehog signaling to continuous variation in facial growth and shape , 2010, Development.

[9]  Ryan M. Anderson,et al.  BMP antagonism protects Nodal signaling in the gastrula to promote the tissue interactions underlying mammalian forebrain and craniofacial patterning. , 2010, Human molecular genetics.

[10]  R. Quiezi,et al.  Holoprosencephaly and holoprosencephaly‐like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients , 2010, American journal of medical genetics. Part A.

[11]  D. Pineda-Alvarez,et al.  A Hypomorphic Allele in the FGF8 Gene Contributes to Holoprosencephaly and Is Allelic to Gonadotropin-Releasing Hormone Deficiency in Humans , 2010, Molecular Syndromology.

[12]  A. Laquérriere,et al.  Neuropathology of holoprosencephaly , 2010, American journal of medical genetics. Part C, Seminars in medical genetics.

[13]  L. Kodjabachian,et al.  Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway , 2010, Development.

[14]  J. Belmont,et al.  Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly. , 2009, Molecular genetics and metabolism.

[15]  G. Oliver,et al.  Pathogenesis of holoprosencephaly. , 2009, The Journal of clinical investigation.

[16]  B. Feldman,et al.  Identification of common and unique modifiers of zebrafish midline bifurcation and cyclopia. , 2009, Developmental biology.

[17]  L. Solnica-Krezel,et al.  Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. , 2008, Developmental cell.

[18]  J. Belmont,et al.  Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly. , 2008, American journal of human genetics.

[19]  Ida M. Washington,et al.  Dose- and route-dependent teratogenicity, toxicity, and pharmacokinetic profiles of the hedgehog signaling antagonist cyclopamine in the mouse. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  J. Hébert,et al.  The ups and downs of holoprosencephaly: dorsal versus ventral patterning forces , 2008, Clinical genetics.

[21]  R. Krauss.  Holoprosencephaly: new models, new insights , 2007, Expert Reviews in Molecular Medicine.

[22]  E. Monuki.  The Morphogen Signaling Network in Forebrain Development and Holoprosencephaly , 2007, Journal of neuropathology and experimental neurology.

[23]  K. Shiota,et al.  Sequential developmental changes in holoprosencephalic mouse embryos exposed to ethanol during the gastrulation period. , 2007, Birth defects research. Part A, Clinical and molecular teratology.

[24]  Toyoaki Tenzen,et al.  The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. , 2007, Genes & development.

[25]  E. Hagos,et al.  BMC Developmental Biology BioMed Central , 2007 .

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

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

[28]  C. Ibáñez,et al.  Synergistic interaction between Gdf1 and Nodal during anterior axis development. , 2006, Developmental biology.

[29]  Diane Hu,et al.  Molecular interactions coordinating the development of the forebrain and face. , 2005, Developmental biology.

[30]  Diane Hu,et al.  Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes. , 2004, The Journal of clinical investigation.

[31]  L. Pasquier,et al.  Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype–phenotype correlations , 2004, Human mutation.

[32]  A. Roberts,et al.  SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. , 2004, Molecular pharmacology.

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

[34]  F. Cole,et al.  Microform Holoprosencephaly in Mice that Lack the Ig Superfamily Member Cdon , 2003, Current Biology.

[35]  Ryan M. Anderson,et al.  Chordin and noggin promote organizing centers of forebrain development in the mouse. , 2002, Development.

[36]  Jussi Taipale,et al.  Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. , 2002, Genes & development.

[37]  S. Chapman,et al.  Analysis of spatial and temporal gene expression patterns in blastula and gastrula stage chick embryos. , 2002, Developmental biology.

[38]  Y. Ohkubo,et al.  Coordinate expression of Fgf8, Otx2, Bmp4, and Shh in the rostral prosencephalon during development of the telencephalic and optic vesicles , 2001, Neuroscience.

[39]  V. Dupé,et al.  Hindbrain patterning involves graded responses to retinoic acid signalling. , 2001, Development.

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

[41]  C. Niehrs,et al.  The role of prechordal mesendoderm in neural patterning , 2001, Current Opinion in Neurobiology.

[42]  Stephen W. Wilson,et al.  The Nodal Pathway Acts Upstream of Hedgehog Signaling to Specify Ventral Telencephalic Identity , 2001, Neuron.

[43]  G. Schoenwolf,et al.  Classification scheme for genes expressed during formation and progression of the avian primitive streak , 2001, The Anatomical record.

[44]  F. Müller,et al.  Direct action of the nodal-related signal cyclops in induction of sonic hedgehog in the ventral midline of the CNS. , 2000, Development.

[45]  P. Beachy,et al.  Genetics of ventral forebrain development and holoprosencephaly. , 2000, Current opinion in genetics & development.

[46]  W. Talbot,et al.  Nodal signaling patterns the organizer. , 2000, Development.

[47]  M. Muenke,et al.  Molecular genetics of holoprosencephaly. , 2000, Frontiers in bioscience : a journal and virtual library.

[48]  K. Jones,et al.  The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. , 1999, Human molecular genetics.

[49]  D. Hu,et al.  The role of sonic hedgehog in normal and abnormal craniofacial morphogenesis. , 1999, Development.

[50]  R. Kapur,et al.  The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. , 1998, Development.

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

[52]  P. Beachy,et al.  Teratogen-mediated inhibition of target tissue response to Shh signaling. , 1998, Science.

[53]  J. Rubenstein,et al.  Patterning of the embryonic forebrain , 1998, Current Opinion in Neurobiology.

[54]  M. Kessel,et al.  Patterning of the chick forebrain anlage by the prechordal plate. , 1997, Development.

[55]  P. Ingham,et al.  one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube. , 1997, Genes and function.

[56]  P. Beachy,et al.  Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function , 1996, Nature.

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

[58]  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.

[59]  V. Hamburger,et al.  A series of normal stages in the development of the chick embryo , 1951, Journal of morphology.

[60]  X. Zhou,et al.  Nodal is a novel TGF-beta-like gene expressed in the mouse node during gastrulation. , 1993, Nature.