Bmi1
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Brian Biehs
PROVIDER: E-GEOD-46001 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Transcriptional profiling of Bmi1 mutant dental epithelia including the stem cell compartment to determine which genes are upregulated in response to loss of Bmi1. Two condition experiment: dental epithelia homozygous null for Bmi1 and WT dental epithelia. 4 replicates each
2013-04-12 | E-GEOD-45999 | biostudies-arrayexpress
Project description:This experiment is aimed at determining the genetic signature of dental stem cell colonies grown in vitro and how that signature changes when Bmi1 activity is removed. Another question to be answered by the experiment is whether Bmi1 has alternate targets besides Ink4a/Arf. There are 12 total samples: 4 biological replicates for each genotype that consist of single colonies grown in vitro.
2013-04-12 | E-GEOD-46000 | biostudies-arrayexpress
Project description:Severe myoclonic epilepsy of infancy (SMEI), or Dravet syndrome (DS), is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development, and persistent drug-resistant seizures. One of its primary monogenic causes is a mutation in SCN1A (Nav1.1), a type I voltage-gated sodium channel. In mice, Nav1.1 mutation is associated with reduced sodium current, altered interneuron firing, cognitive deficits, autistic-like traits and seizures. Here we describe a larval zebrafish Nav1.1 mutant that recapitulates salient features of the human SCN1A mutation phenotype. Between three and seven days post-fertilization, Nav1.1 mutants exhibit spontaneous abnormal electrographic activity, hyperactivity and convulsive behaviors. Transcriptomic analysis of Nav1.1 mutants was remarkable for the relatively small fraction of genes that were differentially expressed (~2%) and the lack of compensatory changes in expression for other SCN subunits. Pharmacological studies confirmed an antiepileptic action for the ketogenic diet, benzodiazepine, valproate, potassium bromide and stiripentol in Nav1.1 mutants; acetazolamide, phenytoin, ethosuximide had no effect, carbamazepine and vigabatrin made seizures worse. Using this mutant, we screened a chemical library of 320 compounds and identified four compounds that reduced spontaneous seizure-like behavior and one compound (clemizole) that inhibited convulsive behavior and electrographic seizures. Drug-resistant scn1a zebrafish mutants described here represent a new direction in modeling pediatric epilepsy and could be used to identify novel lead compounds for DS patients 4 Control sibling samples (sample= 10 pooled larvae) and 4 Nav1.1 mutants (sample= 10 pooled larvae) were collected at 6 dpf (days post fertilization). The Nav1.1 mutants were selected based on phenotype (dark color).
2014-01-04 | E-GEOD-43312 | biostudies-arrayexpress
Project description:Mutation or deletion of LIS1 (Lissencephaly-1) underlies classical lissencephaly, a migration disorder resulting in brain malformation, epilepsy and mental retardation. Orthologues for LIS1 genes (lis1a and lis1b) are ubiquitously expressed in developing zebrafish larvae, but the functional consequences of Lis1 knockdown are unknown. Here we used lis1-specific morpholino oligonucleotides (MOs, targeting protein translation or mRNA splicing, respectively) to transiently knockdown Lis1 expression in zebrafish. Injection of lis1 MOs resulted in morphological changes including microcephaly. At four days post-fertilization, lis1 morphants exhibited spontaneous convulsive behavior and abnormal large-amplitude electrographic discharge resembling that seen in acute and genetic zebrafish models of epilepsy. Abnormal brain development and neuronal migration defects were observed when lis1 MO injections were made into fluorescent reporter lines demarcating interneuron distribution (Dlx5a/6a:GFP) and brain structure (GBT0133:mRFP). Microarray analysis for ~44,000 Danio rerio transcripts identified 215 up-regulated and 160 down-regulated genes. Quantitative PCR and whole-mount in situ hybridization were used to validate these results for twenty and seven genes, respectively. These findings in a simple vertebrate model reproducing neuroanatomical and epileptic hallmarks of the human condition represent a novel approach to the study of childhood seizure disorders associated with a single gene mutation 4 WT samples (sample= 10 pooled larvae) and 4 Lis1Morphants slight phenotype (sample= 10 pooled larvae) were collected at 4dpf (days post fertilization). The morphants were selected based on phenotype and seizure behavior. Both groups of fish derived from same pools of eggs
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Project description:Cell fate is defined by specific transcriptional program. Here, we provide evidence that the transcriptional coactivator, Mediator 1 (MED1), is critical in determining the cell fate of ectodermal epithelia. MED1 ablation disrupted enamel formation and generated hair adjacent to the incisors. Deletion of MED1 altered the differentiation of dental epithelia to one expressing epidermal and hair genes similar to the skin. The cellular switch from dental to epidermal/hair lineage was characterized by abnormalities in MED1 deficient dental epithelial stem cells residing in cervical loop. MED1 deficiency caused a failure of dental epithelial stem cells to commit to the dental stratum intermedium regulated by Notch signaling. Instead, MED1 deficient cells retained stem cell potentials expressing Sox2. These cells were eventually adopted an epidermal fate probably through calcium provided through capillary networks, which is originally utilized for enamel formation. Our results demonstrate that MED1 regulates Sox2/Notch1 regulated cell lineage determination in dental epithelia. Our study also shows a potential to regenerate hairs by using genetically engineered dental tissues or cells outside of the skin. n=3 WT and KO (each sample contain dissected dental tissues from 3 mice combined)
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Project description:Cell fate is defined by specific transcriptional program. Here, we provide evidence that the transcriptional coactivator, Mediator 1 (MED1), is critical in determining the cell fate of ectodermal epithelia. MED1 ablation disrupted enamel formation and generated hair adjacent to the incisors. Deletion of MED1 altered the differentiation of dental epithelia to one expressing epidermal and hair genes similar to the skin. The cellular switch from dental to epidermal/hair lineage was characterized by abnormalities in MED1 deficient dental epithelial stem cells residing in cervical loop. MED1 deficiency caused a failure of dental epithelial stem cells to commit to the dental stratum intermedium regulated by Notch signaling. Instead, MED1 deficient cells retained stem cell potentials expressing Sox2. These cells were eventually adopted an epidermal fate probably through calcium provided through capillary networks, which is originally utilized for enamel formation. Our results demonstrate that MED1 regulates Sox2/Notch1 regulated cell lineage determination in dental epithelia. Our study also shows a potential to regenerate hairs by using genetically engineered dental tissues or cells outside of the skin. n=4 WT and KO (each group contains dissected dental tissues from 3 mice combined)
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Project description:Cell fate is defined by specific transcriptional program. Here, we provide evidence that the transcriptional coactivator, Mediator 1 (MED1), is critical in determining the cell fate of ectodermal epithelia. MED1 ablation disrupted enamel formation and generated hair adjacent to the incisors. Deletion of MED1 altered the differentiation of dental epithelia to one expressing epidermal and hair genes similar to the skin. The cellular switch from dental to epidermal/hair lineage was characterized by abnormalities in MED1 deficient dental epithelial stem cells residing in cervical loop. MED1 deficiency caused a failure of dental epithelial stem cells to commit to the dental stratum intermedium regulated by Notch signaling. Instead, MED1 deficient cells retained stem cell potentials expressing Sox2. These cells were eventually adopted an epidermal fate probably through calcium provided through capillary networks, which is originally utilized for enamel formation. Our results demonstrate that MED1 regulates Sox2/Notch1 regulated cell lineage determination in dental epithelia. Our study also shows a potential to regenerate hairs by using genetically engineered dental tissues or cells outside of the skin. n=3 WT and KO (each sample contain dissected dental tissues from 3 mice combined)
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