Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes

Dario Acampora, Virginia Avantaggiato, Francesca Tuorto, Paolo Barone, Marzia Perera, Daniel Choo, Doris Wu, Giorgio Corte, Antonio Simeone

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c.) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA. Interestingly, homozygous mutant mice (hOtx21/hOtx21) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.

Original languageEnglish
Pages (from-to)1417-1426
Number of pages10
JournalDevelopment
Volume126
Issue number7
Publication statusPublished - Apr 1999

Fingerprint

Phenotype
Telencephalon
Inner Ear
Mesencephalon
Amino Acid Sequence
Epilepsy
Sense Organs
Multiple Abnormalities
Neural Plate
Semicircular Canals
Gastrulation
Rhombencephalon
Prosencephalon
Acoustics
Cerebellum
Genes
Drosophila
Embryonic Structures
Complementary DNA
Proteins

Keywords

  • Cortex
  • Evolution
  • Inner ear
  • Mouse
  • Otx1
  • Otx2
  • Transcriptional control

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Acampora, D., Avantaggiato, V., Tuorto, F., Barone, P., Perera, M., Choo, D., ... Simeone, A. (1999). Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes. Development, 126(7), 1417-1426.

Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes. / Acampora, Dario; Avantaggiato, Virginia; Tuorto, Francesca; Barone, Paolo; Perera, Marzia; Choo, Daniel; Wu, Doris; Corte, Giorgio; Simeone, Antonio.

In: Development, Vol. 126, No. 7, 04.1999, p. 1417-1426.

Research output: Contribution to journalArticle

Acampora, D, Avantaggiato, V, Tuorto, F, Barone, P, Perera, M, Choo, D, Wu, D, Corte, G & Simeone, A 1999, 'Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes', Development, vol. 126, no. 7, pp. 1417-1426.
Acampora D, Avantaggiato V, Tuorto F, Barone P, Perera M, Choo D et al. Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes. Development. 1999 Apr;126(7):1417-1426.
Acampora, Dario ; Avantaggiato, Virginia ; Tuorto, Francesca ; Barone, Paolo ; Perera, Marzia ; Choo, Daniel ; Wu, Doris ; Corte, Giorgio ; Simeone, Antonio. / Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes. In: Development. 1999 ; Vol. 126, No. 7. pp. 1417-1426.
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