title: Pax2 and Pea3 synergize to activate a novel regulatory enhancer for spalt4 in the developing ear.
abstract: The transcription factor spalt4 is a key early-response gene in otic placode induction. Here, we characterize the cis-regulatory regions of spalt4 responsible for activation of its expression in the developing otic placode and report the isolation of a novel core enhancer. Identification and mutational analysis of putative transcription factor binding sites reveal that Pea3, a downstream effector of FGF signaling, and Pax2 directly activate spalt4 during ear development. Morpholino-mediated knock-down of each factor reduces or eliminates reporter expression. In contrast, combined over-expression of Pea3 and Pax2 drives ectopic reporter expression, suggesting that they function synergistically. These studies expand the gene regulatory network underlying early otic development by identifying direct inputs that mediate spalt4 expression.
authors.affiliation: Division of Biology 139-74, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Meyer
authors.initials: M
authors.lastname: Barembaum
authors.forename: Marianne
authors.initials: M
authors.lastname: Bronner-Fraser
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004423:Ear / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor; D014157:Transcription Factors; C484468:spalt protein, vertebrate; C065788:transcription factor PEA3