Monaghan A P, Grau E, Bock D, Schütz G
Division Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg.
Development. 1995 Mar;121(3):839-53. doi: 10.1242/dev.121.3.839.
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.
果蝇无尾基因是孤儿核受体亚家族的成员。在果蝇中,无尾基因是胚胎两极模式形成所必需的。在发育过程中,无尾基因会响应躯干受体酪氨酸激酶信号转导级联反应,在胚胎末端被激活。无尾基因的隐性突变会导致头部前部以及第八腹节之后所有结构出现异常。无尾基因的局部表达需要与另一个末端基因驼背基因共同作用,以控制下游基因的表达。我们分离出了果蝇无尾基因的小鼠同源物,该同源物在DNA结合结构域显示出相当高的同源性,这表明相应的蛋白质结合相似的识别序列。尽管配体结合结构域显示出与无尾基因配体结构域的共同特征,但它也与其他孤儿核受体、人类卵清蛋白上游结合蛋白转录因子(hCOUP-TF I和II)共享保守的氨基酸序列。我们分析了小鼠中无尾基因的表达情况,结果表明,从妊娠第8天开始,它特异性地定位于发育中的前脑,从妊娠第8.75天开始定位于背侧中脑。为了确定表达的前后边界,我们将无尾基因的表达模式与其他前脑标记物的表达模式进行了比较,包括远端缺失基因(Dlx1)、脑因子1(BF1)和正齿状基因(Otx1和Otx2)。除了发育中的前脑,这些基因在两个结构中表现出动态的表达模式,这两个结构的发育需要来自前脑的诱导信号:眼睛和鼻子。这些结果表明,小鼠无尾基因可能是前脑分化模式形成所必需的。