The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain

Abstract

The Drosophila tailless gene is a member of the orphan nuclear receptor subfamily. In Drosophila, the tailless gene is required for pattern formation in embryonic poles. During development, tailless is activated in the termini of the embryo in response to the torso receptor tyrosine kinase signal transduction cascade. Recessive mutations of tailless result in abnormalities in anterior portions of the head and in all structures posterior to the eighth abdominal segment. Localised expression of tailless is required in combination with a second terminal gene, huckebein, to control the expression of downstream genes. We have isolated a mouse homolog of the Drosophila tailless gene, which shows considerable homology in the DNA-binding domain suggesting that the respective proteins bind similar recognition sequences. Although the ligand-binding domain shows features in common with the tailless ligand domain, it also shares conserved amino acid stretches with other orphan nuclear receptors, the human ovalbumin upstream binding protein transcription factors (hCOUP-TF I and II). We have analysed the expression of taillees 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 forebrain markers, including distal-less (Dlx1), brain factor 1 (BF1), and the orthodenticle genes (Otx1 and Otx2). In addition to the developing forebrain, these genes show dynamic patterns of expression in two structures whose development requires inductive signals from the forebrain: the eye and the nose. These results suggest that the mouse taillees gene may be required to pattern anterior brain differentiation.