<b><i>Otx1 </i>function overlaps with <i>Otx2</i> in development of mouse forebrain and midbrain</b>

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<jats:p> <jats:italic>Background: </jats:italic>We previously reported that the homozygous mutation of <jats:italic>Otx2</jats:italic> gene, a mouse cognate of the <jats:italic>Drosophila</jats:italic> head gap gene <jats:italic>orthodenticle</jats:italic>, causes failure in the development of the rostral head anterior to rhombomere 3, which may correspond to earlier <jats:italic>Otx2 </jats:italic>expression in cells destined for the anterior mesoendoderm. At the same time, the <jats:italic>Otx2 </jats:italic>heterozygous mutation displayed a phenotype characterized as otocephaly, probably related to expression in the anterior neuroectoderm at the subsequent pharyngula stage. Defects were characteristic in the most anterior and posterior regions of <jats:italic>Otx2</jats:italic> expression where <jats:italic>Otx1</jats:italic>, another mouse cognate of <jats:italic>orthodenticle</jats:italic>, is not or weakly expressed. They were not found in the region where <jats:italic>Otx1</jats:italic> is expressed.</jats:p><jats:p> <jats:italic>Results: </jats:italic>In the present work, <jats:italic>Otx1</jats:italic> null mutant mice were generated by gene targeting in embryonic stem cells. No defects were apparent in the regionalization of the early embryonic rostral brain. The newborn brain defects were subtle and most likely related to later <jats:italic>Otx1</jats:italic>‐unique expression. <jats:italic>Otx1</jats:italic> and <jats:italic>Otx2</jats:italic> double heterozygous mutant brains, however, exhibited marked defects throughout the fore‐ and midbrains, where defects were not apparent with a single mutation alone.</jats:p><jats:p> <jats:italic>Conclusions:</jats:italic> <jats:italic>Otx1</jats:italic> and <jats:italic>Otx2</jats:italic> play synergistic roles in the development of the forebrain and midbrain where both genes are expressed.</jats:p>

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