title: A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra.
abstract: Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes.
authors.affiliation: Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Glauber
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Dana
authors.forename: Steve S
authors.initials: SS
authors.lastname: Park
authors.forename: David A
authors.initials: DA
authors.lastname: Colby
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Noro
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Fujisawa
authors.forename: A Richard
authors.initials: AR
authors.lastname: Chamberlin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Steele
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D004475:Ectoderm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D006829:Hydra / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D011728:Pyridones / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D060508:Wnt3 Protein / Q000096:biosynthesis
chemical_list: C586204:DAC-2-25; D011728:Pyridones; D054852:Small Molecule Libraries; D060508:Wnt3 Protein; D049452:Green Fluorescent Proteins
keywords: Cnidaria; Hydra; Pattern formation; Pyridone; Regeneration; Small molecule