title: Organizer formation in Hydra is disrupted by thalidomide treatment.
abstract: Thalidomide is a drug that is well known for its teratogenic properties in humans. Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry. Hydra develops asexually via Wnt-dependent organizer formation, leading to the budding of a new organism. We observe both induction and inhibition of organizer formation depending on cellular context. Interestingly, thalidomide treatment altered budding and the developing organizer, but had little effect on the adult. Expression of Hybra1, a marker of the organizer increased upon thalidomide treatment. However when the organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition, thalidomide suppresses induction. We show that inhibition of Wnt signaling is not mediated by induction of the BMP pathway. We show that thalidomide activity on organizer formation in hydra depends on the activity of casein kinase1 and the abundance of β-catenin. Finally, we find that interstitial cells, multipotent cells which give rise to nemoatocytes, neural, digestive and germline cells, are partially responsible for the inhibitory effect of thalidomide.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Room 884, Toronto, Ontario, Canada M5G1X5. maria.brooun@gmail.com
authors.forename: Maria
authors.initials: M
authors.lastname: Brooun
authors.forename: Armen
authors.initials: A
authors.lastname: Manoukian
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Hans R
authors.initials: HR
authors.lastname: Bode
authors.forename: Helen
authors.initials: H
authors.lastname: McNeill
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D047389:Casein Kinase I / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006829:Hydra / Q000196:embryology* / Q000502:physiology; D017403:In Situ Hybridization; D020897:Organizers, Embryonic; D015398:Signal Transduction / Q000187:drug effects; D013723:Teratogens / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D013723:Teratogens; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D013792:Thalidomide; D047389:Casein Kinase I; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3