Otx proteins constitute a class of vertebrate homeodomain-containingtranscription factors that have been shown to be essential for anteriorhead formation, including brain morphogenesis. They are orthologous to theproduct of the Drosophila head gap gene, orthodenticle (Otd), and appear toplay similar roles in both, since the developmental abnormalities caused bydisruption of these transcription factors in one, can be recovered bysubstitution of the factor(s) from the other. Such studies have providedstrong evidence that there exists a conserved genetic programme for insectand mammalian brain development, which presumably arose in a more primitivecommon ancestor [, ].Two vertebrate orthodenticle-related transcription factors have been indentified, Otx1 and Otx2, which have sizes of 355 and 289 residuesrespectively. They contain a bicoid-like homeodomain, which features aconserved lysine residue at position 9 of the DNA recognition helix, whichis thought to confer high-affinity binding to TAATCC/T elements on DNA [].Otd-like transcription factors have also been found in zebrafish and certain lamprey species. Mice completely lacking Otx2 (due to targeted gene disruption) die duringearly embryogenesis. Analysis reveals that they lack the neuroectodermthat is destined to become the forebrain, midbrain and rostral hindbrain.They also show major abnormalities in their body plan. Mice that haveartificially-reduced levels of Otx2 develop head abnormalities reminiscentof otocephaly [].
