Project description:Early dorsal telencephalon development is coordinated by an interplay of transcription factors that exhibit a graded expression pattern in neural progenitors. How they function together to orchestrate cortical development remains largely unknown. The Emx2 and Dmrta2 genes encode TFs that are expressed in a similar caudomedialhigh/ rostrolaterallow gradient in the ventricular zone of the developing dorsal telencephalon with, in the medial pallium, Dmrta2 but not Emx2 expressed in the developing choroid plexus. Their constitutive loss has been shown to impart similar cortical abnormalities, and their combined deletion exacerbates the phenotypes, suggesting possible cooperation during cortex development. In this study, we utilized molecular and genetic approaches to dissect how Emx2 functions with Dmrta2 during cortical development. Our results show that while they regulate a similar set of genes, their common direct targets are limited but include key regulators of cortical development. Identification of the interaction partners of Emx2 suggests that it coordinates with the LIM-domain binding protein Ldb1 to execute the activation and repression of some of its downstream targets. Finally, while Emx2 is known to suppress choroid plexus development, we also provide evidence that Dmrta2 is in contrast required for choroid plexus since in its absence in medial telencephalic progenitors, mice develop hydrocephalous postnatally, a phenotype that appears to be due to a compromised cytoarchitecture. Together, these data indicate that Emx2 and Dmrta2 have similar but also distinct functions in telencephalon development and provide the first insights into Emx2 mechanism of action.
Project description:Early dorsal telencephalon development is coordinated by an interplay of transcription factors that exhibit a graded expression pattern in neural progenitors. How they function together to orchestrate cortical development remains largely unknown. The Emx2 and Dmrta2 genes encode TFs that are expressed in a similar caudomedialhigh/ rostrolaterallow gradient in the ventricular zone of the developing dorsal telencephalon with, in the medial pallium, Dmrta2 but not Emx2 expressed in the developing choroid plexus. Their constitutive loss has been shown to impart similar cortical abnormalities, and their combined deletion exacerbates the phenotypes, suggesting possible cooperation during cortex development. In this study, we utilized molecular and genetic approaches to dissect how Emx2 functions with Dmrta2 during mouse cortical development. Our results show that while they regulate a similar set of genes, their common direct targets are limited but include key regulators of cortical development. The identification of the interaction partners of Emx2 suggests that it coordinates with the LIM-domain binding protein Ldb1 to execute the activation and repression of some of its downstream targets. Finally, while Emx2 is known to suppress choroid plexus development, we also provide evidence that Dmrta2 is, in contrast, required for choroid plexus since in its absence in medial telencephalic progenitors, mice develop hydrocephalus postnatally, a phenotype that appears to be due to a compromised cytoarchitecture. Together, these data indicate that Emx2 and Dmrta2 have similar but also distinct functions in telencephalon development and provide the first insights into Emx2 mechanism of action.
Project description:Early dorsal telencephalon development is coordinated by an interplay of transcription factors that exhibit a graded expression pattern in neural progenitors. How they function together to orchestrate cortical development remains largely unknown. The Emx2 and Dmrta2 genes encode TFs that are expressed in a similar caudomedialhigh/ rostrolaterallow gradient in the ventricular zone of the developing dorsal telencephalon with, in the medial pallium, Dmrta2 but not Emx2 expressed in the developing choroid plexus. Their constitutive loss has been shown to impart similar cortical abnormalities, and their combined deletion exacerbates the phenotypes, suggesting possible cooperation during cortex development. In this study, we utilized molecular and genetic approaches to dissect how Emx2 functions with Dmrta2 during cortical development. Our results show that while they regulate a similar set of genes, their common direct targets are limited but include key regulators of cortical development. Identification of the interaction partners of Emx2 suggests that it coordinates with the LIM-domain binding protein Ldb1 to execute the activation and repression of some of its downstream targets. Finally, while Emx2 is known to suppress choroid plexus development, we also provide evidence that Dmrta2 is in contrast required for choroid plexus since in its absence in medial telencephalic progenitors, mice develop hydrocephalous postnatally, a phenotype that appears to be due to a compromised cytoarchitecture. Together, these data indicate that Emx2 and Dmrta2 have similar but also distinct functions in telencephalon development and provide the first insights into Emx2 mechanism of action.
Project description:Atoh1-Cre; Myc/Myc mice developed choroid plexus papilloma and Atoh1-Cre; Myc/Myc; p53fl/fl mice developed choroid plexus carcinoma. By studying the gene expression profiles of normal choroid plexus, choroid plexus papilloma and choroid plexus carcinoma in mice, we aim to gain a better understanding of the biology of choroid plexus tumors
Project description:We report the transcription profiling of choroid plexus at 4 developmental stages, E12,5, P0, P14 and 6 month. We also compared wildtype and Foxj1-/- choroid plexus transcriptome at P0.
Project description:To understand the genes deregulated in WT us Emx2 Knockout dorsal telencephalon at E12.5. We then performed gene expression profiling analysis using data obtained from RNA-seq of 5 different WT and Emx2KO dorsal telencephalon samples at E12.5
Project description:Gene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy. Choroid plexus tumors are rare pediatric brain tumors derrived from the choroid plexus epithelium. Gene expression profiles of lasermicrodissected tumor cells from 7 individual choroid plexus tumor samples obtained at surgery were compared to gene expression profiles from non-neoplastic choroid plexus epithelial cells lasermicrodissected from normal non-neoplastic choroid plexus obtained at autopsy (Am J Surg Pathol. 2006 Jan;30(1):66-74.) in order to identfy genes differentially expressed in choroid plexus tumor cells.
Project description:Choroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.