Amphi-COUP-TF, a nuclear orphan receptor of the lancelet Branchiostoma floridae, is implicated in retinoic acid signaling pathways

• Published in: Development genes and evolution Vol. 210; pp. 471 - 482
• Main Authors: Langlois, M.C., Vanacker, J.M., Holland, N.D., Escriva, H., Queva, C., Laudet, Vincent, Holland, L.Z.
• Format: Journal Article
• Language: English
• Published: Springer Verlag 2000
• Subjects: Computer Science; Life Sciences; Amphioxus; Transcription factors; Cephalochordate; COUP-TF; Nuclearhormone receptors
• ISSN: 0949-944X; 1432-041X

In vertebrates, the orphan nuclear receptors of the COUP-TF group function as negative transcriptionalregulators that inhibit the hormonal induction of targetgenes mediated by classical members of the nuclear hor-mone superfamily, such as the retinoic acid receptors(RARs) or the thyroid hormone receptors (TRs). To in-vestigate the evolutionary conservation of the roles of COUP-TF receptors as negative regulators in the retinoidand thyroid hormone pathways, we have characterizedAmphiCOUP-TF, the homologue of COUP-TFI andCOUP-TFII, in the chordate amphioxus ( Branchiostoma floridae ), the closest living invertebrate relative of thevertebrates. Electrophoretic mobility shift assays(EMSA) showed that AmphiCOUP-TF binds to a widevariety of response elements, as do its vertebrate homo-logues. Furthermore, AmphiCOUP-TF is a transcription-al repressor that strongly inhibits retinoic acid-mediatedtransactivation. In situ hybridizations revealed expres-sion of AmphiCOUP-TF in the nerve cord of late larvae,in a region corresponding to hindbrain and probably an-terior spinal cord. Although the amphioxus nerve cordappears unsegmented at the gross anatomical level, thispattern reflects segmentation at the cellular level withstripes of expressing cells occurring adjacent to the endsand the centers of each myotomal segment, which mayinclude visceral motor neurons and somatic motor neu-rons respectively, among other cells. A comparison of the expression pattern of AmphiCOUP-TF with those of its vertebrate homologues, suggests that the roles of COUP-TF in patterning of the nerve cord evolved priorto the split between the amphioxus and vertebrate lineag-es. Furthermore, in vitro data also suggest that Amphi-COUP-TF acts as a negative regulator of signalling byother nuclear receptors such as RAR, TR or ER.