title: WNK signaling is involved in neural development via Lhx8/Awh expression.
abstract: WNK kinase family is conserved among many species and regulates SPAK/OSR1 and ion co-transporters. Some mutations in human WNK1 or WNK4 are associated with Pseudohypoaldosteronism type II, a form of hypertension. WNK is also involved in developmental and cellular processes, but the molecular mechanisms underlying its regulation in these processes remain unknown. Here, we identify a new target gene in WNK signaling, Arrowhead and Lhx8, which is a mammalian homologue of Drosophila Arrowhead. In Drosophila, WNK was shown to genetically interact with Arrowhead. In Wnk1 knockout mice, levels of Lhx8 expression were reduced. Ectopic expression of WNK1, WNK4 or Osr1 in mammalian cells induced the expression of the Lhx8. Moreover, neural specification was inhibited by the knockdown of both Wnk1 and Wnk4 or Lhx8. Drosophila WNK mutant caused defects in axon guidance during embryogenesis. These results suggest that WNK signaling is involved in the morphological and neural development via Lhx8/Arrowhead.
authors: Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Sato
authors: Hiroshi
authors: H
authors: Shibuya
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D055495:Neurogenesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D000076204:WNK Lysine-Deficient Protein Kinase 1; D014921:Wings, Animal / Q000033:anatomy & histology
chemical_list: C108601:Awh protein, Drosophila; D017931:DNA Primers; D029721:Drosophila Proteins; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D015778:Minor Histocompatibility Antigens; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498744:Wnk1 protein, mouse
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