title: Differential expression of tropomyosin during segmental heart development in Mexican axolotl.
abstract: The Mexican axolotl, Ambystoma mexicanum, serves as an intriguing model to investigate myofibril organization and heart development in vertebrates. The axolotl has a homozygous recessive cardiac lethal gene "c" which causes a failure of ventricular myofibril formation and contraction. However, the conus of the heart beats, and has organized myofibrils. Tropomyosin (TM), an essential component of the thin filament, has three known striated muscle isoforms (TPM1alpha, TPM1kappa, and TPM4alpha) in axolotl hearts. However, it is not known whether there are differential expression patterns of these tropomyosin isoforms in various segments of the heart. Also, it is not understood whether these isoforms contribute to myofibril formation in a segment-specific manner. In this study, we have utilized anti-sense oligonucleotides to separately knockdown post-transcriptional expression of TPM1alpha and TPM4alpha. We then evaluated the organization of myofibrils in the conus and ventricle of normal and cardiac mutant hearts using immunohistochemical techniques. We determined that the TPM1alpha isoform, a product of the TPM1 gene, was essential for myofibrillogenesis in the conus, whereas TPM4alpha, the striated muscle isoform of the TPM4 gene, was essential for myofibrillogenesis in the ventricle. Our results support the segmental theory of vertebrate heart development.
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, 750 East Adams St., Syracuse, New York 13210, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Zajdel
authors.forename: Matthew D
authors.initials: MD
authors.lastname: McLean
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Denz
authors.forename: Syamalima
authors.initials: S
authors.lastname: Dube
authors.forename: Harold L
authors.initials: HL
authors.lastname: Thurston
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Poiesz
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Dube
mesh_terms: D000558:Ambystoma mexicanum / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development* / Q000502:physiology; D009024:Morphogenesis; D009210:Myofibrils / Q000378:metabolism / Q000648:ultrastructure; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D014335:Tropomyosin