title: Six1 is a key regulator of the developmental and evolutionary architecture of sensory neurons in craniates.
abstract: BACKGROUND
  Various senses and sensory nerve architectures of animals have evolved during adaptation to exploit diverse environments. In craniates, the trunk sensory system has evolved from simple mechanosensory neurons inside the spinal cord (intramedullary), called Rohon-Beard (RB) cells, to multimodal sensory neurons of dorsal root ganglia (DRG) outside the spinal cord (extramedullary). The fish and amphibian trunk sensory systems switch from RB cells to DRG during development, while amniotes rely exclusively on the DRG system. The mechanisms underlying the ontogenic switching and its link to phylogenetic transition remain unknown.
  
  
  RESULTS
  In Xenopus, Six1 overexpression promoted precocious apoptosis of RB cells and emergence of extramedullary sensory neurons, whereas Six1 knockdown delayed the reduction in RB cell number. Genetic ablation of Six1 and Six4 in mice led to the appearance of intramedullary sensory neuron-like cells as a result of medial migration of neural crest cells into the spinal cord and production of immature DRG neurons and fused DRG. Restoration of SIX1 expression in the neural crest-linage partially rescued the phenotype, indicating the cell autonomous requirements of SIX1 for normal extramedullary sensory neurogenesis. Mouse Six1 enhancer that mediates the expression in DRG neurons activated transcription in Xenopus RB cells earlier than endogenous six1 expression, suggesting earlier onset of mouse SIX1 expression than Xenopus during sensory development.
  
  
  CONCLUSIONS
  The results indicated the critical role of Six1 in transition of RB cells to DRG neurons during Xenopus development and establishment of exclusive DRG system of mice. The study provided evidence that early appearance of SIX1 expression, which correlated with mouse Six1 enhancer, is essential for the formation of DRG-dominant system in mice, suggesting that heterochronic changes in Six1 enhancer sequence play an important role in alteration of trunk sensory architecture and contribute to the evolution of the trunk sensory system.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yajima
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Haruki
authors.initials: H
authors.lastname: Ochi
authors.forename: Keiko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamamura
authors.forename: Hajime
authors.initials: H
authors.lastname: Ogino
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Division of Biology, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. kkawakam@jichi.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D005075:Biological Evolution; D002465:Cell Movement; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009432:Neural Crest / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C530879:Six1 protein, Xenopus; C490947:Six1 protein, mouse; C098490:Six4 protein, mouse; D015534:Trans-Activators; D029867:Xenopus Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins