DEVELOPMENTAL REGULATION OF THE ORPHAN RECEPTOR COUP-TF-II GENE IN SPINAL MOTOR-NEURONS

Members of the steroid/thyroid hormone receptor superfamily are involv ed in the control of cell identity and of pattern formation during emb ryonic development. Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) can act as regulators of various steroid/thyroid ho rmone receptor pathways. To begin to study the role of COUP-TFs during embryogenesis, we cloned a chicken COUP-TF (cCOUP-TF II) which is hig hly homologous to human COUP-IF II. Northern analysis revealed high le vels of cCOUP-TF II transcripts during organogenesis. Nuclear extracts from whole embryos and from embryonic spinal cords were used in elect rophoretic mobility shift assays. These assays showed that COUP-TF pro tein is present in these tissues and is capable of binding to a COUP e lement (a direct repeat of AGGTCA with one base pair spacing). Analysi s of cCOUP-TF expression by in situ hybridization revealed high levels of cCOUP-TF II mRNA in the developing spinal motor neurons. Since the ventral properties of the spinal cord, including the development of m otor neurons, is in part established by inductive signals from the not ochord, we transplanted an additional notochord next to the dorsal reg ion of the neural tube in order to induce ectopic motor neurons. We ob served that an ectopic notochord induced cCOUP-TF II gene expression i n the dorsal spinal cord in a region coextensive with ectopic domains of SC1 and Islet-1, two previously identified motor neuron markers. Co llectively, our studies raise the possibility that cCOUP-TF II is invo lved in motor neuron development.