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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
- 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
- Kim, Jin Mahn; Yeon, Ji Hye; Choi, Seong Kyoon; Huh, Yang Hoon; Fang, Zhi; Park, Seo Jin; Kim, Myoung Ok; Ryoo, Zae Young; Kang, Kyeongjin; Kweon, Hee-Seok; Jeon, Won Bae; Li, Chris; Kim, Kyu Hyung
- DGIST Authors
- Jeon, Won Bae; Kim, Kyu Hyung
- Issue Date
- PLoS Genetics, 11(8)
- Article Type
- Article; Caenorhabditis Elegans; Cell Fate; Controlled Study; DNA Sequence; EXPRESSION; FAMILY; FATES; Flp 12 Neuropeptide Gene; Gene; Gene Expression Regulation; Genetic Variability; HOMEOBOX GENE; Human; Human Cell; Interneuron; LHX6 Protein; LHX8; LHX8 Protein; LIM 4 Protein; LIM Protein; Marker Gene; Molecular Evolution; Motoneuron; NemATODE CAENORHABDITIS-ELEGANS; NERVOUS-system; Neuroblastoma Cell; Nonhuman; OLFACTION; Protein Domain; Protein Function; Protein Motif; Protein Targeting; Sensory Nerve Cell; SH-SY5Y; SPECIFICATION; Transcription Factor; Unclassified Drug
- 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. © 2015 Kim et al.
- Public Library of Science
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- Companion Diagnostics and Medical Technology Research Group1. Journal Articles
Department of Brain and Cognitive SciencesThe K. Kim Lab of Neurobehavior and Neural Circuits1. Journal Articles
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