title: The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor Neuron-Type.
abstract: The expression of specific transcription factors determines the differentiated features of postmitotic neurons. However, the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood. In C. elegans, the cholinergic and peptidergic SMB sensory/inter/motor neurons innervate muscle quadrants in the head and control the amplitude of sinusoidal movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal characteristics of the SMB neurons. In lim-4 mutant animals, expression of terminal differentiation genes, such as the cholinergic gene battery and the flp-12 neuropeptide gene, is completely abolished and thus the function of the SMB neurons is compromised. LIM-4 activity promotes SMB identity by directly regulating the expression of the SMB marker genes via a distinct cis-regulatory motif. Two human LIM-4 orthologs, LHX6 and LHX8, functionally substitute for LIM-4 in C. elegans. Furthermore, C. elegans LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in the human neuronal cell lines. Our results indicate that the evolutionarily conserved LIM-4/LHX6 homeodomain proteins function in generation of precise neuronal subtypes.
authors: Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors: Jinmahn
authors: J
authors: Kim
authors: Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors: Jihye
authors: J
authors: Yeon
authors: Laboratory of Biochemistry and Cellular Engineering, Division of NanoBio Technology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors: Seong-Kyoon
authors: SK
authors: Choi
authors: Nano-Bio Electron Microscopy Research Group, Korea Basic Science Institute, Daejeon, Korea.
authors: Yang Hoon
authors: YH
authors: Huh
authors: Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors: Zi
authors: Z
authors: Fang
authors: School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), School of Animal BT Science, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors: Seo Jin
authors: SJ
authors: Park
authors: School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), School of Animal BT Science, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors: Myoung Ok
authors: MO
authors: Kim
authors: School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), School of Animal BT Science, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors: Zae Young
authors: ZY
authors: Ryoo
authors: Department of Anatomy and Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan School of Medicine, Gyeonggi-Do, Korea.
authors: Kyeongjin
authors: K
authors: Kang
authors: Nano-Bio Electron Microscopy Research Group, Korea Basic Science Institute, Daejeon, Korea.
authors: Hee-Seok
authors: HS
authors: Kweon
authors: Laboratory of Biochemistry and Cellular Engineering, Division of NanoBio Technology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors: Won Bae
authors: WB
authors: Jeon
authors: Department of Biology, City College of the City University of New York, New York, New York, United States of America.
authors: Chris
authors: C
authors: Li
authors: Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors: Kyuhyung
authors: K
authors: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D059329:Cholinergic Neurons / Q000378:metabolism; D016384:Consensus Sequence; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D060850:LIM-Homeodomain Proteins / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000502:physiology*; D059467:Transcriptome
chemical_list: D029742:Caenorhabditis elegans Proteins; C121947:LHX6 protein, human; D060850:LIM-Homeodomain Proteins; C120637:Lim-4 protein, C elegans; D009419:Nerve Tissue Proteins; D014157:Transcription Factors