title: The pre-vertebrate origins of neurogenic placodes.
abstract: The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE-derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates.
authors.affiliation: Center for Integrative Genomics, Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
authors.forename: Philip Barron
authors.initials: PB
authors.lastname: Abitua
authors.affiliation: Center for Integrative Genomics, Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
authors.forename: T Blair
authors.initials: TB
authors.lastname: Gainous
authors.affiliation: Center for Integrative Genomics, Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
authors.forename: Angela N
authors.initials: AN
authors.lastname: Kaczmarczyk
authors.affiliation: Center for Integrative Genomics, Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Winchell
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement de Villefranche-sur-mer, Observatoire Océanologique, 06230 Villefranche-sur-mer, France.
authors.forename: Clare
authors.initials: C
authors.lastname: Hudson
authors.affiliation: Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kamata
authors.affiliation: Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Institute for Integrative Neurobiology and Department of Biology, Faculty of Science and Engineering, Konan University, Kobe 658-8501, Japan.
authors.forename: Takehiro G
authors.initials: TG
authors.lastname: Kusakabe
authors.affiliation: Center for Integrative Genomics, Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Levine
mesh_terms: D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins; D002938:Ciona intestinalis / Q000166:cytology* / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014714:Vertebrates / Q000033:anatomy & histology* / Q000196:embryology* / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D007987:Gonadotropin-Releasing Hormone; D017027:Protein Tyrosine Phosphatases