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 language | English |
|---|---|
| Pages (from-to) | 1417-1426 |
| Number of pages | 10 |
| Journal | Development |
| Volume | 126 |
| Issue number | 7 |
| Publication status | Published - Apr 1999 |
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Keywords
- Cortex
- Evolution
- Inner ear
- Mouse
- Otx1
- Otx2
- Transcriptional control
ASJC Scopus subject areas
- Anatomy
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes
AU - Acampora, Dario
AU - Avantaggiato, Virginia
AU - Tuorto, Francesca
AU - Barone, Paolo
AU - Perera, Marzia
AU - Choo, Daniel
AU - Wu, Doris
AU - Corte, Giorgio
AU - Simeone, Antonio
PY - 1999/4
Y1 - 1999/4
N2 - 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.
AB - 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.
KW - Cortex
KW - Evolution
KW - Inner ear
KW - Mouse
KW - Otx1
KW - Otx2
KW - Transcriptional control
UR - http://www.scopus.com/inward/record.url?scp=0032941091&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032941091&partnerID=8YFLogxK
M3 - Article
C2 - 10068635
AN - SCOPUS:0032941091
VL - 126
SP - 1417
EP - 1426
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 7
ER -