The pre-vertebrate origins of neurogenic placodes

Nature. 2015 Aug 27;524(7566):462-5. doi: 10.1038/nature14657. Epub 2015 Aug 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Bone Morphogenetic Proteins
  • Ciona intestinalis / cytology*
  • Ciona intestinalis / embryology*
  • Ciona intestinalis / genetics
  • Ciona intestinalis / metabolism
  • Ectoderm / metabolism
  • Gonadotropin-Releasing Hormone / metabolism
  • HEK293 Cells
  • Homeodomain Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Larva / cytology
  • Larva / metabolism
  • Molecular Sequence Data
  • Neurons / cytology*
  • Neurons / metabolism
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Vertebrates / anatomy & histology*
  • Vertebrates / embryology*
  • Vertebrates / physiology


  • Bone Morphogenetic Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • Gonadotropin-Releasing Hormone
  • Protein Tyrosine Phosphatases

Associated data

  • GENBANK/KR902348