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. 1993 Jul;12(7):2735–2747. doi: 10.1002/j.1460-2075.1993.tb05935.x

A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo.

A Simeone 1, D Acampora 1, A Mallamaci 1, A Stornaiuolo 1, M R D'Apice 1, V Nigro 1, E Boncinelli 1
PMCID: PMC413524  PMID: 8101484

Abstract

We studied the expression of two vertebrate homeobox genes, Otx1 and Otx2, related to orthodenticle, a gene expressed in the developing head of Drosophila. Both genes are expressed in restricted regions of the developing rostral brain including the presumptive cerebral cortex and olfactory bulbs. The expression patterns of the two genes in diencephalon suggest that they both have a role in establishing the boundary between presumptive dorsal and ventral thalamus. They are also expressed in regions of the developing olfactory, auricolar and ocular system, including the covering of the optic nerve. Otx1 expression is detectable from day 8 of gestation in telencephalic, diencephalic and mesencephalic regions. From day 10.5 of gestation its expression extends to some metencephalic areas. Otx2 appears to be already expressed in the epiblast of prestreak embryos. It persists in the entire embryonic ectoderm for some time after the onset of gastrulation. In midstreak embryos its expression appears progressively restricted to the anterior embryonic ectoderm corresponding to presumptive fore- and mid-brain. In early midgestation embryos it is expressed in telencephalic, diencephalic and mesencephalic regions but from day 11.75 of gestation its expression disappears from dorsal telencephalon and is confined to diencephalic and mesencephalic regions. Otx2 is one of the earliest genes expressed in the epiblast and immediately afterwards is expressed in anterior neuroectoderm, demarcating rostral brain regions even before headfold formation. Its gene product contains a homeodomain of the bicoid class and is able to recognize and transactivate a bicoid target sequence.

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Selected References

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  1. Acampora D., D'Esposito M., Faiella A., Pannese M., Migliaccio E., Morelli F., Stornaiuolo A., Nigro V., Simeone A., Boncinelli E. The human HOX gene family. Nucleic Acids Res. 1989 Dec 25;17(24):10385–10402. doi: 10.1093/nar/17.24.10385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akam M. The molecular basis for metameric pattern in the Drosophila embryo. Development. 1987 Sep;101(1):1–22. [PubMed] [Google Scholar]
  3. Andrews P. W. Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell line in vitro. Dev Biol. 1984 Jun;103(2):285–293. doi: 10.1016/0012-1606(84)90316-6. [DOI] [PubMed] [Google Scholar]
  4. Bastian H., Gruss P. A murine even-skipped homologue, Evx 1, is expressed during early embryogenesis and neurogenesis in a biphasic manner. EMBO J. 1990 Jun;9(6):1839–1852. doi: 10.1002/j.1460-2075.1990.tb08309.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blumberg B., Wright C. V., De Robertis E. M., Cho K. W. Organizer-specific homeobox genes in Xenopus laevis embryos. Science. 1991 Jul 12;253(5016):194–196. doi: 10.1126/science.1677215. [DOI] [PubMed] [Google Scholar]
  6. Boncinelli E., Simeone A., Acampora D., Mavilio F. HOX gene activation by retinoic acid. Trends Genet. 1991 Oct;7(10):329–334. doi: 10.1016/0168-9525(91)90423-n. [DOI] [PubMed] [Google Scholar]
  7. Cohen S. M., Jürgens G. Mediation of Drosophila head development by gap-like segmentation genes. Nature. 1990 Aug 2;346(6283):482–485. doi: 10.1038/346482a0. [DOI] [PubMed] [Google Scholar]
  8. Cohen S., Jürgens G. Drosophila headlines. Trends Genet. 1991 Aug;7(8):267–272. doi: 10.1016/0168-9525(91)90327-M. [DOI] [PubMed] [Google Scholar]
  9. Dalton D., Chadwick R., McGinnis W. Expression and embryonic function of empty spiracles: a Drosophila homeo box gene with two patterning functions on the anterior-posterior axis of the embryo. Genes Dev. 1989 Dec;3(12A):1940–1956. doi: 10.1101/gad.3.12a.1940. [DOI] [PubMed] [Google Scholar]
  10. Driever W., Nüsslein-Volhard C. The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell. 1988 Jul 1;54(1):95–104. doi: 10.1016/0092-8674(88)90183-3. [DOI] [PubMed] [Google Scholar]
  11. Driever W., Nüsslein-Volhard C. The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature. 1989 Jan 12;337(6203):138–143. doi: 10.1038/337138a0. [DOI] [PubMed] [Google Scholar]
  12. Dush M. K., Martin G. R. Analysis of mouse Evx genes: Evx-1 displays graded expression in the primitive streak. Dev Biol. 1992 May;151(1):273–287. doi: 10.1016/0012-1606(92)90232-6. [DOI] [PubMed] [Google Scholar]
  13. Finkelstein R., Perrimon N. The molecular genetics of head development in Drosophila melanogaster. Development. 1991 Aug;112(4):899–912. doi: 10.1242/dev.112.4.899. [DOI] [PubMed] [Google Scholar]
  14. Finkelstein R., Smouse D., Capaci T. M., Spradling A. C., Perrimon N. The orthodenticle gene encodes a novel homeo domain protein involved in the development of the Drosophila nervous system and ocellar visual structures. Genes Dev. 1990 Sep;4(9):1516–1527. doi: 10.1101/gad.4.9.1516. [DOI] [PubMed] [Google Scholar]
  15. Frohman M. A., Boyle M., Martin G. R. Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development. 1990 Oct;110(2):589–607. doi: 10.1242/dev.110.2.589. [DOI] [PubMed] [Google Scholar]
  16. Hanes S. D., Brent R. DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9. Cell. 1989 Jun 30;57(7):1275–1283. doi: 10.1016/0092-8674(89)90063-9. [DOI] [PubMed] [Google Scholar]
  17. Kessel M., Gruss P. Murine developmental control genes. Science. 1990 Jul 27;249(4967):374–379. doi: 10.1126/science.1974085. [DOI] [PubMed] [Google Scholar]
  18. Klämbt C., Jacobs J. R., Goodman C. S. The midline of the Drosophila central nervous system: a model for the genetic analysis of cell fate, cell migration, and growth cone guidance. Cell. 1991 Feb 22;64(4):801–815. doi: 10.1016/0092-8674(91)90509-w. [DOI] [PubMed] [Google Scholar]
  19. Lawson K. A., Meneses J. J., Pedersen R. A. Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development. 1991 Nov;113(3):891–911. doi: 10.1242/dev.113.3.891. [DOI] [PubMed] [Google Scholar]
  20. McGinnis W., Krumlauf R. Homeobox genes and axial patterning. Cell. 1992 Jan 24;68(2):283–302. doi: 10.1016/0092-8674(92)90471-n. [DOI] [PubMed] [Google Scholar]
  21. Price M., Lazzaro D., Pohl T., Mattei M. G., Rüther U., Olivo J. C., Duboule D., Di Lauro R. Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain. Neuron. 1992 Feb;8(2):241–255. doi: 10.1016/0896-6273(92)90291-k. [DOI] [PubMed] [Google Scholar]
  22. Price M., Lemaistre M., Pischetola M., Di Lauro R., Duboule D. A mouse gene related to Distal-less shows a restricted expression in the developing forebrain. Nature. 1991 Jun 27;351(6329):748–751. doi: 10.1038/351748a0. [DOI] [PubMed] [Google Scholar]
  23. Simeone A., Acampora D., Gulisano M., Stornaiuolo A., Boncinelli E. Nested expression domains of four homeobox genes in developing rostral brain. Nature. 1992 Aug 20;358(6388):687–690. doi: 10.1038/358687a0. [DOI] [PubMed] [Google Scholar]
  24. Simeone A., Acampora D., Nigro V., Faiella A., D'Esposito M., Stornaiuolo A., Mavilio F., Boncinelli E. Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells. Mech Dev. 1991 Mar;33(3):215–227. doi: 10.1016/0925-4773(91)90029-6. [DOI] [PubMed] [Google Scholar]
  25. Simeone A., Gulisano M., Acampora D., Stornaiuolo A., Rambaldi M., Boncinelli E. Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex. EMBO J. 1992 Jul;11(7):2541–2550. doi: 10.1002/j.1460-2075.1992.tb05319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tam P. P. Regionalisation of the mouse embryonic ectoderm: allocation of prospective ectodermal tissues during gastrulation. Development. 1989 Sep;107(1):55–67. doi: 10.1242/dev.107.1.55. [DOI] [PubMed] [Google Scholar]
  27. Thali M., Müller M. M., DeLorenzi M., Matthias P., Bienz M. Drosophila homoeotic genes encode transcriptional activators similar to mammalian OTF-2. Nature. 1988 Dec 8;336(6199):598–601. doi: 10.1038/336598a0. [DOI] [PubMed] [Google Scholar]
  28. Walldorf U., Gehring W. J. Empty spiracles, a gap gene containing a homeobox involved in Drosophila head development. EMBO J. 1992 Jun;11(6):2247–2259. doi: 10.1002/j.1460-2075.1992.tb05284.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wieschaus E., Perrimon N., Finkelstein R. orthodenticle activity is required for the development of medial structures in the larval and adult epidermis of Drosophila. Development. 1992 Jul;115(3):801–811. doi: 10.1242/dev.115.3.801. [DOI] [PubMed] [Google Scholar]
  30. Wilkinson D. G., Bhatt S., Cook M., Boncinelli E., Krumlauf R. Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature. 1989 Oct 5;341(6241):405–409. doi: 10.1038/341405a0. [DOI] [PubMed] [Google Scholar]

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