Otx genes in the development and evolution of the vertebrate brain.
Most of the gene candidates for the control of developmental programmes that underlie brain morphogenesis in vertebrates are the orthologues of Drosophila genes coding for signalling molecules or transcription factors. Among these, the orthodenticle group, including the Drosophila orthodenticle (otd) and the vertebrate Otx1 and Otx2 genes, is mostly involved in fundamental processes of anterior neural patterning. In mouse, Drosophila and intermediate species otd/Otx genes have shown a remarkable similarity in expression pattern suggesting that they could be part of a conserved control system operating in the brain and different from that coded by the HOX complexes controlling the hindbrain and spinal cord. In order to verify this hypothesis, a series of mouse models have been generated in which the functions of the murine Otx genes were: (i) fully inactivated, (ii) replaced with each other, and (iii) replaced with the Drosophila otd gene. The data obtained highlight a crucial role for the Otx genes in specification, regionalization and terminal differentiation of rostral central nervous system and lead to hypothesize that modification of their regulatory control may have influenced the morphogenesis and evolution of the brain.
Boyl
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MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, New Hunt's House, SE1 1UL, London, UK.
Signore
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M
Annino
A
A
Barbera
J P
JP
Acampora
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D
Simeone
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A
D000483:Alleles; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000196:embryology*; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins; D005314:Embryonic and Fetal Development / Q000235:genetics; D004827:Epilepsy / Q000235:genetics; D019143:Evolution, Molecular; D005326:Fetal Proteins / Q000235:genetics / Q000502:physiology; D005775:Gastrula / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D051857:Otx Transcription Factors; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012665:Semicircular Canals / Q000196:embryology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014714:Vertebrates / Q000196:embryology / Q000235:genetics*; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
D018076:DNA, Complementary; D029721:Drosophila Proteins; D005326:Fetal Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C497655:OTX1 protein, human; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; C497657:Otx1 protein, Xenopus; C497656:Otx1 protein, mouse; C497661:Otx2 protein, Xenopus; C497660:Otx2 protein, mouse; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; C093053:oc protein, Drosophila