OTX1 compensates for OTX2 requirement in regionalisation of anterior neuroectoderm.
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 (hOtx1(2FL)) replacing only the coding sequence and introns of Otx2 with the human Otx1 codogenic sequence. hOtx1(2FL/2FL) and hOtx1(2FL/-) 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.
Acampora
Dario
D
MRC Centre for Developmental Neurobiology, New Hunt's House, 4th Floor, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
Annino
Alessandro
A
Puelles
Eduardo
E
Alfano
Ivan
I
Tuorto
Francesca
F
Simeone
Antonio
A
D000818:Animals; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004475:Ectoderm / Q000502:physiology*; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008636:Mesencephalon / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D051857:Otx Transcription Factors; D051762:PAX2 Transcription Factor; D010641:Phenotype; D016548:Prosencephalon / Q000196:embryology*; D012333:RNA, Messenger; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; C496456:FGF8 protein, human; C496457:Fgf8 protein, mouse; C084958:GBX2 protein, human; C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C497655:OTX1 protein, human; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; C497656:Otx1 protein, mouse; C497660:Otx2 protein, mouse; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C497319:Pax2 protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors