title: The epigenetic modifier DNMT3A is necessary for proper otic placode formation.
abstract: Cranial placodes are thickenings in the ectoderm that give rise to sensory organs and peripheral ganglia of the vertebrate head. At gastrula and neurula stages, placodal precursors are intermingled in the neural plate border with future neural and neural crest cells. Here, we show that the epigenetic modifier, DNA methyl transferase (DNMT) 3A, expressed in the neural plate border region, influences development of the otic placode which will contribute to the ear. DNMT3A is expressed in the presumptive otic region at gastrula through neurula stages and later in the otic placode itself. Whereas neural plate border and non-neural ectoderm markers Erni, Dlx5, Msx1 and Six1 are unaltered, DNMT3A loss of function leads to early reduction in the expression of the key otic placode specifier genes Pax2 and Gbx2 and later otic markers Sox10 and Soho1. Reduction of Gbx2 was first observed at HH7, well before loss of other otic markers. Later, this translates to significant reduction in the size of the otic vesicle. Based on these results, we propose that DNMT3A is important for enabling the activation of Gbx2 expression, necessary for normal development of the inner ear.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: roellig@caltech.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Roellig
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: mbronner@caltech.edu.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
mesh_terms: D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000502:physiology*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D007758:Ear, Inner / Q000196:embryology* / Q000502:physiology*; D004475:Ectoderm / Q000378:metabolism; D047108:Embryonic Development; D044127:Epigenesis, Genetic; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology; D017403:In Situ Hybridization; D009432:Neural Crest / Q000196:embryology; D054258:Neural Plate / Q000378:metabolism / Q000502:physiology; D051762:PAX2 Transcription Factor / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor; D051761:Paired Box Transcription Factors; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: DNMT3A; Gbx2; Otic; Pax2; Placode
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