title: Thyroid hormone and retinoid X receptor function and expression during sea lamprey (Petromyzon marinus) metamorphosis.
abstract: Sea lampreys (Petromyzon marinus) are members of the ancient class Agnatha and undergo a metamorphosis that transforms blind, sedentary, filter-feeding larvae into free-swimming, parasitic juveniles. Thyroid hormones (THs) appear to be important for lamprey metamorphosis, however, serum TH concentrations are elevated in the larval phase, decline rapidly during early metamorphosis and remain low until metamorphosis is complete; these TH fluctuations are contrary to those of other metamorphosing vertebrates. Moreover, thyroid hormone synthesis inhibitors (goitrogens) induce precocious metamorphosis and exogenous TH treatments disrupt natural metamorphosis in P. marinus. Given that THs exert their effects by binding to TH nuclear receptors (TRs) that often act as heterodimers with retinoid X receptors (RXRs), we cloned and characterized these receptors from P. marinus and examined their expression during metamorphosis. Two TRs (PmTR1 and PmTR2) and three RXRs (PmRXRs) were isolated from P. marinus cDNA. Phylogenetic analyses group the PmTRs together on a branch prior to the gnathostome TRα/β split. The three RXRs also group together, but our data indicated that these transcripts are most likely either allelic variants of the same gene locus, or the products of a lamprey-specific duplication event. Importantly, these P. marinus receptors more closely resemble vertebrate as opposed to invertebrate chordate receptors. Functional analysis revealed that PmTR1 and PmTR2 can activate transcription of TH-responsive genes when treated with nanomolar concentrations of TH and they have distinct pharmacological profiles reminiscent of vertebrate TRβ and TRα, respectively. Also similar to other metamorphosing vertebrates, expression patterns of the PmTRs during lamprey metamorphosis suggest that PmTR1 has a dynamic, tissue-specific expression pattern that correlates with tissue morphogenesis and biochemical changes and PmTR2 has a more uniform expression pattern. This TR expression data suggests that THs, either directly or via a metabolite, may function to positively modulate changes at the tissue or organ levels during lamprey metamorphosis. Collectively the results presented herein support the hypothesis that THs have a dual functional role in the lamprey life cycle whereby high levels promote larval feeding, growth and lipogenesis and low levels promote metamorphosis.
authors.affiliation: Department of Zoology and Division of Life Sciences, University of Toronto, Toronto, ON M1A 1C4, Canada.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Manzon
authors.affiliation: Department of Zoology and Division of Life Sciences, University of Toronto, Toronto, ON M1A 1C4, Canada.
authors.forename: John H
authors.initials: JH
authors.lastname: Youson
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, École Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Holzer
authors.affiliation: Cellular and Developmental Laboratory, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Staiano
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, École Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudet
authors.affiliation: Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada. Electronic address: richard.manzon@uregina.ca.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Manzon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000502:physiology*; D008969:Molecular Sequence Data; D048428:Petromyzon / Q000502:physiology*; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D047488:Retinoid X Receptors; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta
keywords: Lamprey; Metamorphosis; Phylogenetic analyses; Retinoid X receptors; Thyroid hormone nuclear receptors