MOUSE OTX2 FUNCTIONS IN THE FORMATION AND PATTERNING OF ROSTRAL HEAD

The anterior part of the vertebrate head expresses a group of homeo bo x genes in segmentally restricted patterns during embryogenesis. Among these, Otx2 expression covers the entire fore- and midbrains and take s place earliest. To examine its role in development of the rostral he ad, a mutation was introduced into this locus. The homozygous mutants did not develop structures anterior to rhombomere 3, indicating an ess ential role of Otx2 in the formation of the rostral head. In contrast, heterozygous mutants displayed craniofacial malformations designated as otocephaly; affected structures appeared to correspond to the most posterior and most anterior domains of Otx expression where Otx1 is no t expressed. The home- and heterozygous mutant phenotypes suggest Otx2 functions as a gap-like gene in the rostral head where Hox code is no t present. The evolutionary significance of Otx2 mutant phenotypes was discussed for the innovation of the neurocranium and the jaw.