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Patterns of gene expression associated with Pten deficiency in the developing inner ear.

Kim HJ, Ryu J, Woo HM, Cho SS, Sung MK, Kim SC, Park MH, Park T, Koo SK - PLoS ONE (2014)

Bottom Line: We identified 46 statistically significant transcripts using significance analysis of microarrays, with the false-discovery rate set at 0%.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).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, South Korea.

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.

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Microarray analysis identifies novel Pten targets.Heat maps for relative gene expression of interest (FDR = 0) obtained from three microarrays comparing Pten cKO to wild-type embryos. Green and red indicate decreased and increased expression, respectively, in Pten cKO mice.
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pone-0097544-g001: Microarray analysis identifies novel Pten targets.Heat maps for relative gene expression of interest (FDR = 0) obtained from three microarrays comparing Pten cKO to wild-type embryos. Green and red indicate decreased and increased expression, respectively, in Pten cKO mice.

Mentions: Recently, we reported that Pten cKO mice showed severe abnormalities in neuronal maintenance with increased production of hair cells during inner ear development [15]. To identify the changes caused by Pten deficiency-induced regulation of genes in the developing inner ear, we analyzed DEGs within inner ears at E14.5. Using SAM analysis, we identified a total of 46 transcripts with an FDR = 0 that significantly distinguished the wild-type and Pten cKO groups. Among the transcripts, 45 genes were upregulated and one was downregulated in Pten cKO mice, and are listed in Table 1. While the patterns of gene expression between Pten cKO and wild-type samples were highly similar according to pair-wise comparisons with correlation coefficients (data not shown), 46 DEGs were significantly selected, and their segregation was clearly shown by clustering analysis of a heat map (Fig. 1).


Patterns of gene expression associated with Pten deficiency in the developing inner ear.

Kim HJ, Ryu J, Woo HM, Cho SS, Sung MK, Kim SC, Park MH, Park T, Koo SK - PLoS ONE (2014)

Microarray analysis identifies novel Pten targets.Heat maps for relative gene expression of interest (FDR = 0) obtained from three microarrays comparing Pten cKO to wild-type embryos. Green and red indicate decreased and increased expression, respectively, in Pten cKO mice.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043736&req=5

pone-0097544-g001: Microarray analysis identifies novel Pten targets.Heat maps for relative gene expression of interest (FDR = 0) obtained from three microarrays comparing Pten cKO to wild-type embryos. Green and red indicate decreased and increased expression, respectively, in Pten cKO mice.
Mentions: Recently, we reported that Pten cKO mice showed severe abnormalities in neuronal maintenance with increased production of hair cells during inner ear development [15]. To identify the changes caused by Pten deficiency-induced regulation of genes in the developing inner ear, we analyzed DEGs within inner ears at E14.5. Using SAM analysis, we identified a total of 46 transcripts with an FDR = 0 that significantly distinguished the wild-type and Pten cKO groups. Among the transcripts, 45 genes were upregulated and one was downregulated in Pten cKO mice, and are listed in Table 1. While the patterns of gene expression between Pten cKO and wild-type samples were highly similar according to pair-wise comparisons with correlation coefficients (data not shown), 46 DEGs were significantly selected, and their segregation was clearly shown by clustering analysis of a heat map (Fig. 1).

Bottom Line: We identified 46 statistically significant transcripts using significance analysis of microarrays, with the false-discovery rate set at 0%.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).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, South Korea.

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.

Show MeSH
Related in: MedlinePlus