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JOURNAL ARTICLES
Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation
D. Acampora, V. Avantaggiato, F. Tuorto, P. Briata, G. Corte, A. Simeone
Development 1998 125: 5091-5104;

Summary

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, contribute to brain morphogenesis. In particular Otx1 null mice are viable and show spontaneous epileptic seizures and abnormalities affecting the dorsal telencephalic cortex. Otx2 null mice die early in development and fail in specification of the rostral neuroectoderm and proper gastrulation. In order to determine whether Otx1(−/−)and Otx2(−/−) highly divergent phenotypes reflect differences in temporal expression or biochemical activity of OTX1 and OTX2 proteins, the Otx2-coding sequence was replaced by a human Otx1 full-coding cDNA. Homozygous mutant embryos recovered anterior neural plate and proper gastrulation but failed to maintain forebrain-midbrain identities, displaying a headless phenotype from 9 days post coitum (d.p.c.) onwards. Unexpectedly, in spite of the RNA distribution in both visceral endoderm (VE) and epiblast, the hOTX1 protein was synthesized only in the VE. This VE-restricted translation was sufficient to recover Otx2 requirements for specification of the anterior neural plate and proper organization of the primitive streak, thus providing evidence that the difference between Otx1 and Otx2 null mice phenotypes originates from their divergent expression patterns. Moreover, our data lead us to hypothesize that the differential post-transcriptional control existing between VE and epiblast cells may potentially contribute to fundamental regulatory mechanisms required for head specification.

REFERENCES

    1. Acampora D.,
    2. Mazan S.,
    3. Lallemand Y.,
    4. Avantaggiato V.,
    5. Maury M.,
    6. Simeone A.,
    7. Brûlet P.
    (1995) Forebrain and midbrain regions are deleted Otx2/ mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121, 3279–3290
    OpenUrlAbstract
    1. Acampora D.,
    2. Mazan S.,
    3. Avantaggiato V.,
    4. Barone P.,
    5. Tuorto F.,
    6. Lallemand Y.,
    7. Brûlet P.,
    8. Simeone A.
    (1996) Epilepsy and brain abnormalities in mice lacking Otx1 gene. Nature Genet 14, 218–222
    OpenUrlCrossRefPubMedWeb of Science
    1. Acampora D.,
    2. Avantaggiato V.,
    3. Tuorto F.,
    4. Simeone A.
    (1997) Genetic control of brain morphogenesis through Otx gene dosage requirement. Development 124, 3639–3650
    OpenUrlAbstract
    1. Acampora D.,
    2. Mazan S.,
    3. Tuorto F.,
    4. Avantaggiato V.,
    5. Tremblay J. J.,
    6. Lazzaro D.,
    7. di Carlo A.,
    8. Mariano A.,
    9. Macchia P. E.,
    10. Corte G.,
    11. Macchia V.J.,
    12. Drouin J.,
    13. Brûlet P.,
    14. Simeone A.
    (1998) Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescentstage-specific control of pituitary levels of GH, FSH and LH. Development 125, 1061–1072
    OpenUrl
    1. Ang S.-L.,
    2. Conlon R. A.,
    3. Jin O.,
    4. Rossant J.
    (1994) Positive and negative signals from mesoderm regulate the expression of mouse Otx2 in ectoderm explants. Development 120, 2979–2989
    OpenUrlAbstract
    1. Ang S.-L.,
    2. Jin O.,
    3. Rhinn M.,
    4. Daigle N.,
    5. Stevenson L.,
    6. Rossant J.
    (1996) Targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. Development 122, 243–252
    OpenUrlAbstract
    1. Avantaggiato V.,
    2. Acampora D.,
    3. Tuorto F.,
    4. Simeone A.
    (1996) Retinoic acid induces stage-specific repatterning of the rostral central nervous system. Dev. Biol 175, 347–357
    OpenUrlCrossRefPubMedWeb of Science
    1. Barnes J. D.,
    2. Crosby J. L.,
    3. Jones C. M.,
    4. Wright C. V.,
    5. Hogan B. L.
    (1994) Embryos expression of Lim-1, the mouse homolog of Xenopus Xlim-1, suggests a role in lateral mesoderm differentiation and neurogenesis. Dev. Biol 161, 167–178
    OpenUrl
    1. Beddington R. S. P.
    (1994) Induction of a second neural axis by the mouse node. Development 120, 613–620
    OpenUrlAbstract
    1. Belo J. A.,
    2. Bouwmeester T.,
    3. Leyns L.,
    4. Kertesz N.,
    5. Gallo M.,
    6. Gollettie M.,
    7. De Robertis E. M.
    (1997) Cerberus - like is a secreted factor with neuralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Mech. Dev 68, 45–57
    OpenUrlCrossRefPubMedWeb of Science
    1. Bouwmeester T.,
    2. Kim S. H.,
    3. Sasai Y.,
    4. Lu B.,
    5. De Robertis E. M.
    (1996) Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer. Nature 382, 595–601
    OpenUrlCrossRefPubMed
    1. Chapman G.,
    2. Remiszeski J. L.,
    3. Webb G. C.,
    4. Schultz T. C.,
    5. Bottema C. D.,
    6. Rathjen P. D.
    (1997) The mouse homeobox gene, Gbx2: genomic organization and expression in pluripotent cells in vitro and in vivo. Genomics 46, 223–233
    OpenUrlCrossRefPubMedWeb of Science
    1. Chen S.,
    2. Wang Q.-L.,
    3. Nie Z.,
    4. Sun H.,
    5. Lennon G.,
    6. Copeland N. G.,
    7. Gilbert D. J.,
    8. Jenkins N. A.,
    9. Zack D. J.
    (1997) Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 19, 1017–1030
    OpenUrlCrossRefPubMedWeb of Science
    1. Crossley P. H.,
    2. Martinez S.,
    3. Martin G. R.
    (1996) Midbrain development induced by FGF8 in the chick embryo. Nature 380, 66–68
    OpenUrlCrossRefPubMed
    1. Dattani M. T.,
    2. Martinez-Barbera J.-P.,
    3. Thomas P. Q.,
    4. Brickman J. M.,
    5. Gupta R.,
    6. Mårtensson I.-L.,
    7. Toresson H.,
    8. Fox M.,
    9. Wales J. K. H.,
    10. Hindmarsh P. C.,
    11. Krauss S.,
    12. Beddington R. S. P.,
    13. Robinson I. C. A. F.
    (1998) Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat. Genet 19, 125–133
    OpenUrlCrossRefPubMedWeb of Science
    1. Doniach T.
    (1993) Planar and vertical induction of anteroposterior pattern during the development of the amphibian central nervous system. J. Neurobiol 24, 1256–1276
    OpenUrlCrossRefPubMedWeb of Science
    1. Finkelstein R.,
    2. Boncinelli E.
    (1994) From fly head to mammalian forebrain: the story of otd and Otx. Trends Genet 10, 310–315
    OpenUrlCrossRefPubMedWeb of Science
    1. Foley A. C.,
    2. Storey K. G.,
    3. Stern C. D.
    (1997) The prechordal region lacks neural inducing ability, but can confer anterior character to more posterior neuroepithelium. Development 124, 2983–2996
    OpenUrlAbstract
    1. Frantz G. D.,
    2. Weimann J. M.,
    3. Levin M. E.,
    4. McConnell S. K.
    (1994) Otx1 and Otx2 define layers and regions in developing cerebral cortex and cerebellum. J. Neurosci 14, 5725–5740
    OpenUrlAbstract
    1. Freud C. L.,
    2. Gregory-Evans C. Y.,
    3. Kurukawa T.,
    4. Papaioannou M.,
    5. Looser J.,
    6. Ploder L.,
    7. Bellingham J.,
    8. Ng D.,
    9. Herbrick J.-A. S.,
    10. Duncan A.,
    11. Scherer S. W.,
    12. Tsui L.-C.,
    13. Loutradis-Anagnostou A.,
    14. Jacobson S. G.,
    15. Cepko C. L.,
    16. Bhattacharya S. S.,
    17. McInnes R. R.
    (1997) Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell 91, 543–553
    OpenUrlCrossRefPubMedWeb of Science
    1. Gurdon J. B.
    (1987) Embryonic induction—molecular prospects. Development 99, 285–306
    OpenUrlPubMedWeb of Science
    1. Houart C.,
    2. Westerfield M.,
    3. Wilson S. W.
    (1998) A small population of anterior cells patterns the forebrain during zebrafish gastrulation. Nature 391, 788–792
    OpenUrlCrossRefPubMed
    1. Joyner A. L.
    (1996) Engrailed, Wnt and Pax genes regulate midbrain-hindbrain development. Trends Genet 12, 15–20
    OpenUrlCrossRefPubMedWeb of Science
    1. Izpisùa-Belmonte J. C.,
    2. De Robertis E. M.,
    3. Storey K. G.,
    4. Stern C. D.
    (1993) The homeobox gene goosecoid and the origin of the organizer cells in the early chick blastoderm. Cell 74, 645–659
    OpenUrlCrossRefPubMedWeb of Science
    1. Lemaire P.,
    2. Kodjabachian L.
    (1996) The vertebrate organizer: structure and molecules. Trends Genet 12, 525–531
    OpenUrlCrossRefPubMedWeb of Science
    1. Li H.,
    2. Tao W.,
    3. Lai E.
    (1996) Characterization of the structure andfunction of the gene for transcription factor BF-1, an essential regulator of forebrain development. Brain Res. Mol. Brain Res 37, 96–104
    OpenUrlPubMed
    1. Logan C.,
    2. Hanks M. C.,
    3. Noble-Topham S.,
    4. Nallainathan D.,
    5. Provart N. J.,
    6. Joyner A. L.
    (1992) Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions. Dev. Genet 13, 345–358
    OpenUrlCrossRefPubMedWeb of Science
    1. Lumsden A.,
    2. Krumlauf R.
    (1996) Patterning the vertebrate neuraxis. Science 274, 1109–1115
    OpenUrlAbstract/FREE Full Text
    1. Mallamaci A.,
    2. Di Blas E.,
    3. Briata P.,
    4. Boncinelli E.,
    5. Corte G.
    (1996) OTX2 homeoprotein in the developing central nervous system and migratory cells of the olfactory area. Mech. Dev 58, 165–178
    OpenUrlCrossRefPubMedWeb of Science
    1. Matsuo I.,
    2. Kuratani S.,
    3. Kimura C.,
    4. Takeda N.,
    5. Aizawa S.
    (1995) Mouse Otx2 functions in the formation and patterning of rostral head. Genes Dev 9, 2646–2658
    OpenUrlAbstract/FREE Full Text
    1. McMahon J. A.,
    2. Takada S.,
    3. Zimmerman L. B.,
    4. Fan C.-M.,
    5. Harland R. M.,
    6. McMahon A. P.
    (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12, 1438–1452
    OpenUrlAbstract/FREE Full Text
    1. Millet S.,
    2. Bloch-Gallego E.,
    3. Simeone A.,
    4. Alvarado-Mallart R.-M.
    (1996) Is the caudal limit of Otx2 gene expression a marker of the midbrain/hindbrain boundary? A study using a chick- Otx2 riboprobe and chick/quail homotopic grafts. Development 122, 3785–3797
    OpenUrlAbstract
    1. Oliver G.,
    2. Mailhos A.,
    3. Wehr R.,
    4. Copeland N. G.,
    5. Jenkins N. A.,
    6. Gruss P.
    (1995) Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045–4055
    OpenUrlAbstract
    1. Rhinn M.,
    2. Dierich A.,
    3. Shawlot W.,
    4. Behringer R. R.,
    5. Le Meur M.,
    6. Ang S.-L.
    (1998) Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. Development 125, 845–856
    OpenUrlAbstract
    1. Rowitch D. H.,
    2. McMahon A. P.
    (1995) Pax-2 expression in the murine neural plate precedes and encompasses the expression domains of Wnt1 and En1. Mech. Dev 52, 3–8
    OpenUrlCrossRefPubMedWeb of Science
    1. Rubenstein J. L. R.,
    2. Shimamura K.,
    3. Martinez S.,
    4. Puelles L.
    (1998) Regionalization of the prosencephalic neural plate. Annu. Rev. Neurosci 21, 445–477
    OpenUrlCrossRefPubMedWeb of Science
    1. Ruiz i Altaba A.
    (1993) Induction and axial patterning of the neural plate: planar and vertical signals. J. Neurobiol 24, 1276–1304
    OpenUrlCrossRefPubMedWeb of Science
    1. Ruiz i Altaba A.
    (1994) Pattern formation in the vertebrate neural plate. Trends Neurosci 17, 233–243
    OpenUrlCrossRefPubMedWeb of Science
    1. Ruiz i Altaba A.
    (1998) Deconstructing the organizers. Nature 391, 748–749
    OpenUrlCrossRefPubMed
    1. Shawlot W.,
    2. Behringer R. R.
    (1995) Requirement for Lim1 in head organizer function. Nature 374, 425–430
    OpenUrlCrossRefPubMed
    1. Simeone A.,
    2. Acampora D.,
    3. Gulisano M.,
    4. Stornaiuolo A.,
    5. Boncinelli E.
    (1992) Nested expression domains of four homeobox genes in developing rostral brain. Nature 358, 687–690
    OpenUrlCrossRefPubMed
    1. Simeone A.,
    2. Acampora D.,
    3. Mallamaci A.,
    4. Stornaiuolo A.,
    5. D'Apice M. R.,
    6. Nigro V.,
    7. Boncinelli E.
    (1993) A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J 12, 2735–2747
    OpenUrlPubMedWeb of Science
    1. Simeone A.,
    2. Avantaggiato V.,
    3. Moroni M. C.,
    4. Mavilio F.,
    5. Arra C.,
    6. Cotelli F.,
    7. Nigro V.,
    8. Acampora D.
    (1995) Retinoic acid induces stage-specific antero-posterior transformation of rostral central nervous system. Mech. Dev 51, 83–98
    OpenUrlCrossRefPubMedWeb of Science
    1. Smith W. C.,
    2. Harland R. M.
    (1992) Expression cloning of noggin, a new dorsalizing factor localized to the Spemann orgnaizer in Xenopus embryos. Cell 70, 829–840
    OpenUrlCrossRefPubMedWeb of Science
    1. Stern C. D.
    (1992) Mesoderm induction and development of the embryonic axis in amniotes. Trends Genet 8, 158–163
    OpenUrlCrossRefPubMed
    1. Tam P. P. L.,
    2. Behringer R. R.
    (1997) Mouse gastrulation: the formation of a mammalian body plan. Mech. Dev 68, 3–25
    OpenUrlCrossRefPubMedWeb of Science
    1. Thomas P.,
    2. Beddington R.
    (1996) Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo. Curr. Biol 6, 1487–1496
    OpenUrlCrossRefPubMedWeb of Science
    1. Varlet I.,
    2. Collignon J.,
    3. Robertson E. J.
    (1997) nodal expression in the primitive endoderm is required for specification of the anterior axis during mouse gastrulation. Development 124, 1033–1044
    OpenUrlAbstract
    1. Waddington C. H.
    (1932) Experiments on the development of chick and duck embryos, cultivated in vitro. Phil. Trans. Roy. Soc. Lond. B 221, 179–230
    OpenUrlFREE Full Text
    1. Wassarman K. M.,
    2. Lewandoski M.,
    3. Campbell K.,
    4. Joyner A. L.,
    5. Rubenstein J. L. R.,
    6. Martinez S.,
    7. Martin G. R.
    (1997) Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. Development 124, 2923–2934
    OpenUrlAbstract
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JOURNAL ARTICLES
Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation
D. Acampora, V. Avantaggiato, F. Tuorto, P. Briata, G. Corte, A. Simeone
Development 1998 125: 5091-5104;
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