Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA102565 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and non-cell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1 (myrAkt) in transgenic mice. Contrary to mice overexpressing wilt type Akt1 (Aktwt), these myrAkt mice display, in a dose-dependent manner, altered development of ectodermally derived organs such as hair, teeth, nails and epidermal glands. To identify the possible molecular mechanisms underlying these alterations, gene profiling approaches were employed. We demonstrate that constitutive Akt activity disturbs the bone morphogenetic protein (BMP)-dependent signaling pathway, which leads to alterations in adult epidermal stem cells. Collectively, we show that epithelial tissue development and homeostasis is dependent on proper regulation of Akt expression and activity. Keywords: ectodermal development, Akt1, skin, transgenic mice
2007-10-25 | GSE9054 | GEO
Project description:The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that decrease neural crest formation, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits PI3K/Akt signaling specifically in FGF-stimulated cells, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest development.
2017-08-17 | GSE95813 | GEO
Project description:The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that decrease neural crest formation, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits PI3K/Akt signaling specifically in FGF-stimulated cells, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest development.
2017-08-17 | GSE95814 | GEO
Project description:Aberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and non-cell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1; (myrAkt) in transgenic mice. Contrary to mice overexpressing wilt type Akt1 (Aktwt), these myrAkt mice display, in a dose-dependent manner, altered development of ectodermally derived organs such as hair, teeth, nails and epidermal glands. To identify the possible molecular mechanisms underlying these alterations, gene profiling approaches were employed. We demonstrate that constitutive Akt activity disturbs the bone morphogenetic protein (BMP)-dependent signaling pathway, which leads to alterations in adult epidermal stem cells. Collectively, we show that epithelial tissue development and homeostasis is dependent on proper regulation of Akt expression and activity. Experiment Overall Design: Two (transgenic mice L60, L84 and LA) or three pools (control mice LC) from RNA whole skin extracts of same genotype were done and analyzed, individually, in mouse microarrays. Comparison was performed between the 4 different genotypes.
2008-06-16 | E-GEOD-9054 | biostudies-arrayexpress
Project description:In addition to driving tumorigenesis, oncogenes can create metabolic vulnerabilities in cancer cells. Here, we tested how the oncogenes AKT and MYC affect the ability to shift between respiration and glycolysis. Using immortalized mammary epithelial cellsMCF10A, we discovered constitutively active AKT but not MYC induced cell death in galactose culture, where cells must rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were short-lived, and AKT-expressing cells recommenced growth after ~15 days in galactose culture. To identify the mechanisms regulating AKT-mediated cell death, we first used metabolomics and found that AKT cells dying in galactose culture exhibited upregulated glutathione metabolism. Next, using shotgun proteomics, we discovered AKT cells dying in galactose upregulated proteins related to nonsense-mediated mRNA decay (NMD), a known response to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered galactose culture induced ROS only in cells expressing AKT. Additionally, we found thatdiscovered the ROS scavenger catalase rescued AKT-expressing cells from galactose culture-induced cell death. We then demonstrated that breast cancer cell lines with constitutively active AKT signaling also exhibited cell death in galactose culture and rescue by catalase. Together, our results demonstrate that AKT but not MYC induces a metabolic vulnerability in cancer cells, namely the that restricted flexibility to use oxidative phosphorylation.
2020-03-19 | PXD015122 | Pride
Project description:To explore the mechanisms downstream of NOTCH1 and PTEN in the control of leukemia cell growth, we performed expression profiling on NOTCH1 induced and Pten-positive T-ALL tumor cells infected with constitutively active AKT (myristoylated-AKT). Constitutive activation of AKT rescues the transcriptional programs induced by NOTCH1 inhibition in Pten-positive T-ALL cells We performed microarray gene expression analysis of GSI treatment in Pten WT NOTCH1 induced leukemias infected with constitutively active AKT (myristoylated-AKT) or empty vector.
2015-08-31 | E-GEOD-71089 | biostudies-arrayexpress
Project description:In order to isolate novel genes regulating neural induction, we utilized a DNA microarray approach. As neural induction is thought to occur via the inhibition of BMP signaling, BMP signaling was inhibited in ectodermal cells by overexpression of a dominant-negative receptor. RNAs were isolated from control animal cap explants and from dominant-negative BMP receptor expressing animal caps and subjected to a microarray experiment using newly generated high-density Xenopus DNA microarray chips. Keywords = neural induction Keywords = BMP Keywords = nervous system Keywords = Xenopus Keywords = microarray
2010-06-10 | E-GEOD-2266 | biostudies-arrayexpress
Project description:Xenopus embryonic ectodermal cells are responsive to various inducing factors. Mesoderm is specified and patterned by extracellular factors including FGF, Nodal, BMP and Wnt families. Pinhead is another secreted protein implicated in mesoderm formation. We found that Pinhead physically interacts with and antagonizes ADMP (anti-dorsalizing morphogenetic protein) that acts as BMP-like protein to promote ventral mesoderm formation. ADMP and BMPs have been shown to cooperate to activate phospho-Smad1 signaling to lead to ventral mesoderm development. Since Chordin is a BMP antagonist, we hypothesized that Pinhead together with Chordin can promote downregulation of phospho-Smad1 signaling that leads to dorsal mesoderm development. RNA sequencing revealed that Pinhead and Chordin synergize in dorsal mesoderm formation in ectodermal explants.
2021-04-19 | GSE168370 | GEO
Project description:Unlike other signaling proteins, cellular stimulation does not induce nuclear AKT accumulation. While AKT1 is cytoplasmic, shifting to the plasma membrane upon stimulation, AKT2 is mainly nuclear. AKT3 in cancer cells is constitutively active at the nuclear envelope, where it phosphorylates TSC2 and promotes proliferation.
2022-12-11 | PXD037856 | Pride
Project description:In order to isolate novel genes regulating neural induction, we utilized a DNA microarray approach. As neural induction is thought to occur via the inhibition of BMP signaling, BMP signaling was inhibited in ectodermal cells by overexpression of a dominant-negative receptor. RNAs were isolated from control animal cap explants and from dominant-negative BMP receptor expressing animal caps and subjected to a microarray experiment using newly generated high-density Xenopus DNA microarray chips. Keywords = neural induction Keywords = BMP Keywords = nervous system Keywords = Xenopus Keywords = microarray Keywords: parallel sample
2005-03-05 | GSE2266 | GEO