title: Activation of Six1 Expression in Vertebrate Sensory Neurons.
abstract: SIX1 homeodomain protein is one of the essential key regulators of sensory organ development. Six1-deficient mice lack the olfactory epithelium, vomeronasal organs, cochlea, vestibule and vestibuloacoustic ganglion, and also show poor neural differentiation in the distal part of the cranial ganglia. Simultaneous loss of both Six1 and Six4 leads to additional abnormalities such as small trigeminal ganglion and abnormal dorsal root ganglia (DRG). The aim of this study was to understand the molecular mechanism that controls Six1 expression in sensory organs, particularly in the trigeminal ganglion and DRG. To this end, we focused on the sensory ganglia-specific Six1 enhancer (Six1-8) conserved between chick and mouse. In vivo reporter assays using both animals identified an important core region comprising binding consensus sequences for several transcription factors including nuclear hormone receptors, TCF/LEF, SMAD, POU homeodomain and basic-helix-loop-helix proteins. The results provided information on upstream factors and signals potentially relevant to Six1 regulation in sensory neurons. We also report the establishment of a new transgenic mouse line (mSix1-8-NLSCre) that expresses Cre recombinase under the control of mouse Six1-8. Cre-mediated recombination was detected specifically in ISL1/2-positive sensory neurons of Six1-positive cranial sensory ganglia and DRG. The unique features of the mSix1-8-NLSCre line are the absence of Cre-mediated recombination in SOX10-positive glial cells and central nervous system and ability to induce recombination in a subset of neurons derived from the olfactory placode/epithelium. This mouse model can be potentially used to advance research on sensory development.
authors: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors: Shigeru
authors: S
authors: Sato
authors: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors: Hiroshi
authors: H
authors: Yajima
authors: Animal Resource Development Unit and Genetic Engineering Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), Kobe, Hyogo, Japan.
authors: Yasuhide
authors: Y
authors: Furuta
authors: Division of Biology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors: Keiko
authors: K
authors: Ikeda
authors: Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors: Kiyoshi
authors: K
authors: Kawakami
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000096:biosynthesis* / Q000235:genetics; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D055757:SOXE Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology*
chemical_list: D030161:Avian Proteins; D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D055757:SOXE Transcription Factors; C490947:Six1 protein, mouse; C098490:Six4 protein, mouse; C527924:Sox10 protein, mouse; D015534:Trans-Activators