Malformations of cortical development are the underlying eitiology of many cases of Mental Retardation and Epilepsy. Subtle, below the resolution of current MRI, cortical dysplasias are probably involved in many cases of MR, Epilepsy and Autism for which no diagnosis can currently be made. Therefore, understanding the process of cortical development will be vital in diagnosing and eventual treatment of many patients with these conditions. More specifically, the cortex forms from two major populations of neuroblasts which reach their final destination in the cortex by differerent mechanisms. One is radial migration from ventricular neuroblasts to the cortical plate. These cells are excititory projection neurons and glia. The second pathway is from the ventral ganglionic eminences and tangential migration of the interneuronal population of primarily inhibitory neurons. Much less is known about the control of the latter process, and many of these currently undiagnosed subtle malformations may stem from abnormalities of this tangential migration. This project focuses on the understanding the control of the tangentially migrating inhibitory interneurons.
Identification of Arx transcriptional targets in the developing basal forebrain.
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View SamplesArx is a paired-box homeodomain transcription factor and the vertebrate ortholog to the Drosophila aristaless (al) gene. Mutations in Arx are associated with a variety of human diseases, including X-linked infantile spasm syndrome (OMIM: 308350), X-linked myoclonic epilepsy with mental retardation and spasticity (OMIM: 300432), X-linked lissencephaly with ambiguous genitalia (OMIM: 300215), X-linked mental retardation 54 (OMIM: 300419), and agenesis of the corpus callosum with abnormal genitalia (OMIM: 300004). Arx-deficient mice exhibit a complex, pleiotrophic phenotype, including decreased proliferation of neuroepithelial cells of the cortex, dysgenesis of the thalamus and olfactory bulbs, and abnormal nonradial migration of GABAergic interneurons. It has been suggested that deficits in interneuron specification, migration, or function lead to loss of inhibitory neurotransmission, which then fails to control excitatory activity and leads to epilepsy or spasticities. Given that Arx mutations are associated with developmental disorders in which epilepsy and spasticity predominate and that Arx-deficient mice exhibit deficits in interneuron migration, understanding the function of Arx in interneuron migration will prove crucial to understanding the pathology underlying interneuronopathies. Yet, downstream transcriptional targets of Arx, to date, remain unidentified.
Identification of Arx transcriptional targets in the developing basal forebrain.
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View SamplesEffect of NF-kB inhibition and activation on gene expression in mouse and human lung cancer cell-lines.
Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance.
Cell line
View SamplesAnalysis of 143 completely histologically-normal breast tissues resulted in the identification of a malignancy risk gene signature that may serve as a marker of subsequent risk of breast cancer development.
Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue.
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View SamplesThe role of different proteins, Always Early (Aly), Spermatocyte Arrest (Sa), Ubi-p63E (Magn) on the gene expression in spermatocyte differentation was assessed by microarray
The polyubiquitin gene Ubi-p63E is essential for male meiotic cell cycle progression and germ cell differentiation in Drosophila.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival.
Disease stage, Cell line
View SamplesWe treated 8 human ovarian cancer cell lines with cisplatin in treatment/recovery cycles to induce in-vitro resistance to the drug. Microarrays measured gene expression at baseline and after each dose schedule (after recovery).
BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival.
Cell line
View SamplesBackground. Genome-wide expression changes are associated with development of chemoresistance in patients with ovarian cancer (OVCA); the BCL2 antagonist of cell death (BAD) apoptosis pathway may play a role in clinical outcome.
BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival.
Disease stage
View SamplesTranscriptome analysis of LDBM cells stimulated with IL-5
IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Specimen part
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