title: Patterns of gene expression associated with Pten deficiency in the developing inner ear.
abstract: In inner ear development, phosphatase and tensin homolog (PTEN) is necessary for neuronal maintenance, such as neuronal survival and accurate nerve innervations of hair cells. We previously reported that Pten conditional knockout (cKO) mice exhibited disorganized fasciculus with neuronal apoptosis in spiral ganglion neurons (SGNs). To better understand the genes and signaling networks related to auditory neuron maintenance, we compared the profiles of differentially expressed genes (DEGs) using microarray analysis of the inner ear in E14.5 Pten cKO and wild-type mice. We identified 46 statistically significant transcripts using significance analysis of microarrays, with the false-discovery rate set at 0%. Among the DEGs, expression levels of candidate genes and expression domains were validated by quantitative real-time RT-PCR and in situ hybridization, respectively. Ingenuity pathway analysis using DEGs identified significant signaling networks associated with apoptosis, cellular movement, and axon guidance (i.e., secreted phosphoprotein 1 (Spp1)-mediated cellular movement and regulator of G-protein signaling 4 (Rgs4)-mediated axon guidance). This result was consistent with the phenotypic defects of SGNs in Pten cKO mice (e.g., neuronal apoptosis, abnormal migration, and irregular nerve fiber patterns of SGNs). From this study, we suggest two key regulatory signaling networks mediated by Spp1 and Rgs4, which may play potential roles in neuronal differentiation of developing auditory neurons.
authors.affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, South Korea.
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, South Korea.
authors.forename: Jihee
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, South Korea.
authors.forename: Hae-Mi
authors.initials: HM
authors.lastname: Woo
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, South Korea.
authors.forename: Samuel Sunghwan
authors.initials: SS
authors.lastname: Cho
authors.affiliation: Korean BioInformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Sung
authors.affiliation: Korean BioInformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, South Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, South Korea; Department of Statistics, Seoul National University, Seoul, South Korea.
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, South Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Koo
mesh_terms: D000818:Animals; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020710:RGS Proteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; C098799:RGS4 protein; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse