Project description:We then examined the mutant mice that lack both Dmrt3 and Dmrta2 alleles, and found the size of the medial cortex including the hippocampus and the cortical hem was significantly reduced in mutant brains .To further investigate how Dmrt3 and Dmrta2 are involved in the development of the medial cortex, we applied gene expression profiling approach using whole genome DNA microarray to identify genes which are differentially expressed in Dmrt3/Dmrta2-knockdown cells. Cortical cells knocked-down both Dmrt3 and Dmrta2 exhibited a dramatic increase of Pax6 expression in the medial cortex, leading to the precocious neuronal differentiation, and simultaneous knockdown of Pax6 with Dmrt3/Dmrta2 rescued the phenotype. Our results unveil a key mechanism that mammalian Dmrt factors maintain more proliferative potential of neural progenitors by suppressing Pax6 expression in the developing cerebral cortex.
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 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:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.