THE MOUSE HOMOLOG OF THE ORPHAN NUCLEAR RECEPTOR TAILLESS IS EXPRESSED IN THE DEVELOPING FOREBRAIN

The Drosophila tailless gene is a member of the orphan nuclear recepto r subfamily. In Drosophila, the tailless gene is required for pattern formation in embryonic poles. During development, tailless is activate d in the termini of the embryo in response to the torso receptor tyros ine kinase signal transduction cascade. Recessive mutations of tailles s result in abnormalities in anterior portions of the head and in all structures posterior to the eighth abdominal segment, Localised expres sion of tailless is required in combination with a second terminal gen e, huckebein, to control the expression of downstream genes. We have i solated a mouse homolog of the Drosophila tailless gene, which shows c onsiderable homology in the DNA-binding domain suggesting that the res pective proteins bind similar recognition sequences. Although the liga nd-binding domain shows features in common with the tailless ligand do main, it also shares conserved amino acid stretches with other orphan nuclear receptors, the human ovalbumin upstream binding protein transc ription factors (hCOUP-TF I and II), We have analysed the expression o f tailless in mice, and show that it is specifically localised to the developing forebrain from day 8 p.c. and in dorsal midbrain from day 8 .75 p.c. To define the anterior and posterior boundaries of expression , we compared the expression pattern of tailless to those of other for ebrain markers, including distal-less (Dlx1), brain factor 1 (BF1), an d the orthodenticle genes (Otx1 and Otx2). In addition to the developi ng forebrain, these genes show dynamic patterns of expression in two s tructures whose development requires inductive signals from the forebr ain: the eye and the nose. These results suggest that the mouse taille ss gene may be required to pattern anterior brain differentiation.