OTX1 compensates for OTX2 requirement in regionalisation of anterior neuroectoderm

Dario Acampora, Alessandro Annino, Eduardo Puelles, Ivan Alfano, Francesca Tuorto, Antonio Simeone

Research output: Contribution to journalArticlepeer-review

Abstract

Otx genes play a relevant role in specification, maintenance and patterning of anterior neuroectoderm. OTX1 and OTX2 proteins share extensive codogenic similarity even though in OTX1 these regions of homology are separated by stretches of amino acid insertions. From 1 to 3 somites stage onwards, Otx1 and Otx2 are largely coexpressed, but only Otx2 is expressed during gastrulation. To determine whether OTX1 and OTX2 gene products share common biochemical properties, mouse models replacing Otx1 with Otx2 and vice versa have been generated. These studies have indicated a remarkable functional equivalence between the two proteins. Nevertheless, it was still debated whether OTX1 is functionally equivalent to OTX2 in early anterior neuroectoderm. To address this issue we generated a new mouse model (hOtx12FL) replacing only the coding sequence and introns of Otx2 with the human Otx1 codogenic sequence. hOtx12FL/2FL and hOtx12FL/- mice were viable, fertile and exhibited an apparently normal behaviour. hOtx1 mRNA was correctly transcribed under the Otx2 transcriptional control and, similarly, the hOTX1 protein was properly distributed and quantitatively very similar if not identical to that of OTX2. Patterning and regionalisation of forebrain and midbrain were unaffected as revealed by the expression of diagnostic genes which are highly sensitive to reduction of OTX proteins, such as Fgf8, Pax2 and Gbx2.

Original languageEnglish
Pages (from-to)497-501
Number of pages5
JournalGene Expression Patterns
Volume3
Issue number4
DOIs
Publication statusPublished - Aug 2003

Keywords

  • Brain patterning
  • Epiblast
  • Functional equivalence
  • Gastrulation
  • Gene replacement
  • Neuroectoderm
  • Otx1
  • Otx2
  • Regionalisation
  • Visceral endoderm

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

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