title: Six1 promotes a placodal fate within the lateral neurogenic ectoderm by functioning as both a transcriptional activator and repressor.
abstract: Cranial placodes, which give rise to sensory organs in the vertebrate head, are important embryonic structures whose development has not been well studied because of their transient nature and paucity of molecular markers. We have used markers of pre-placodal ectoderm (PPE) (six1, eya1) to determine that gradients of both neural inducers and anteroposterior signals are necessary to induce and appropriately position the PPE. Overexpression of six1 expands the PPE at the expense of neural crest and epidermis, whereas knock-down of Six1 results in reduction of the PPE domain and expansion of the neural plate, neural crest and epidermis. Using expression of activator and repressor constructs of six1 or co-expression of wild-type six1 with activating or repressing co-factors (eya1 and groucho, respectively), we demonstrate that Six1 inhibits neural crest and epidermal genes via transcriptional repression and enhances PPE genes via transcriptional activation. Ectopic expression of neural plate, neural crest and epidermal genes in the PPE demonstrates that these factors mutually influence each other to establish the appropriate boundaries between these ectodermal domains.
authors.affiliation: Department of Anatomy and Cell Biology, Institute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USA.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Brugmann
authors.forename: Petra D
authors.initials: PD
authors.lastname: Pandur
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Kenyon
authors.forename: Francesca
authors.initials: F
authors.lastname: Pignoni
authors.forename: Sally A
authors.initials: SA
authors.lastname: Moody
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D004475:Ectoderm / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins; D006609:High Mobility Group Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D007633:Keratins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D016366:Open Reading Frames; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D024002:HMGB Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D007633:Keratins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012313:RNA; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D029867:Xenopus Proteins; C501121:Dlx5 protein, Xenopus; C491016:Dlx6 protein, Xenopus; C527788:Sox3 protein, Xenopus; C112757:Zic2 protein, Xenopus; C491003:foxd3b-A protein, Xenopus; C091023:gro protein, Drosophila; C112522:six2 protein, Xenopus; C527781:sox2 protein, Xenopus