Janet Rossant

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..If Mash2 functions in other aspects of trophoblast development, it must act cooperatively with other factors...

..Furthering our understanding of mouse trophoblast development should provide novel insights into human placental function...

..The exact relationship between lineage segregation, preimplantation polarities and the postimplantation axes remain to be determined but are now open to molecular and cellular investigation...

..Integrated, multidisciplinary programs will be needed to fully exploit the power of the mouse in molecular medicine...

..Manipulation of both intrinsic and extrinsic regulators may be needed to reveal the full potential of stem cells from other stages of development and the adult...

..Further understanding of the complexities of the pathways should help refine such strategies...

..Whether these asymmetries are causally related to embryonic patterning or are coincidental outcomes of the topology of normal development remains uncertain...

..Each illustrates how the availability of the genome sequence will change the way mouse biologists do business in future...

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..These results provide a comprehensive stem cell proteomic resource and enable new approaches to interrogate the mechanisms that regulate cell fate specification...

..In addition, we found that nuclear beta-catenin and other molecular markers are asymmetrically expressed by 4.5 days...

..Therefore, we propose three distinct regions within the mouse notochord, each with unique morphogenetic origins...

..These findings establish that Hh uses both VEGF- and Notch-dependent and -independent mechanisms to pattern specific events in early blood vascular development...

..Thus, Cdx2 is essential for segregation of the ICM and TE lineages at the blastocyst stage by ensuring repression of Oct4 and Nanog in the TE...

..Brg1 is also required for these processes, suggesting that BAF complexes are key components of nuclear Notch signaling. We propose a critical role for Baf60c in Notch-dependent transcription and LR asymmetry...

..Cdx2 therefore appears to act downstream of the first lineage decision, suggesting that processes influencing lineage allocation or morphogenesis may regulate Cdx2 expression along the inside/outside axis of the embryo...

..In conclusion, VEGF-A function through Flk1 mediates survival (and not proliferative or fate change) effects on NSCs, specifically...

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..We propose a model in which the ICM develops as a mosaic of EPI and PE progenitors at E3.5, dependent on Grb2-Ras-MAP kinase signaling, followed by later segregation of the progenitors into the appropriate cell layers...

..Taken together, these data confirm the importance of Porcn for Wnt secretion and gastrulation and suggest that disruption of early development underlies the male lethality of human PORCN mutants...

..These targets are evidence that Nmyc is a regulator of genes involved in mRNA processing and a repressor of the imprinted gene Igf2r in the developing lung...

..Thus, Foxh1 and Nkx2-5 functionally interact and are essential for development of the AHF and its derivatives, the RV and OFT, in response to TGFbeta-like signals...

..This functional genomic approach allows the rapid identification of functionally important components of embryonic development from large datasets of putative targets...

..This study provides new insights about the genetic and cellular basis of the patterning role and development of the early trophoblast...

..We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent molecular mechanisms in the origins of this disease...

..Together, these results demonstrate a key role for VEGF-A production in the podocyte for mesangial cell survival and differentiation...

..They also show that Cdx2 expression is strongly linked to apical membrane polarization...

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..In sum, these results demonstrate that Lfng functions to enhance Notch signaling in myofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation...

..The entire data are available as a web-accessible database to guide the informed development of mouse models to study human disease...

..This molecular compendium, fully accessible via a searchable web-browser interface, serves as a reliable reference of the expressed tissue and organelle proteomes of a leading model mammal...

..We have also demonstrated that activated Fps/Fes causes hemangioma formation in vivo, independently of Flk1, as a result of increasing vascular progenitor density...

..Together, these data indicate that Zfp206 is a regulator of ES cell differentiation that controls a set of genes expressed very early in development, most of which themselves appear to be regulators...

..The gene appears to be important in the integration of the pathways controlling embryonic axial elongation, and anterior-posterior patterning...

..Thus, Flk1 expression marks progenitors with broad mesodermal potential but is not absolutely required for the development of all mesodermal lineages in which it is expressed...

..Finally, we used EOS selection to establish Rett syndrome-specific mouse and human iPS cell lines with known mutations in MECP2...

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..A greater understanding of the similarities and differences between mouse and human preimplantation development has implications for improving assisted reproductive technologies and for deriving human embryonic stem cells...

..GenRate also detected tens of thousands of potential new exons and reconciled discrepancies in current cDNA databases by 'stitching' new transcribed regions into previously annotated genes...

..Together, these studies show that an open chromatin architecture is established in the embryonic lineages during development and is sufficient to distinguish pluripotent cells from tissue-restricted progenitor cells...

..These studies indicate that histone modification mechanisms may differ between early embryo lineages and emphasize the importance of examining in vivo and in vitro progenitor cells...

..In conclusion, we propose a model in which stochastic and progressive specification of EPI and PE lineages occurs during maturation of the blastocyst in an FGF/MAP kinase signal-dependent manner...

..We also discuss the continuing debate that surrounds the relative impacts of early lineage bias versus the stochastic allocation of cells with respect to the events that pattern the blastocyst and initiate its later asymmetries...

..Rescued embryos show severe anterior truncations, indicating a second important role for Smad4 in anterior patterning during embryogenesis...

..Understanding how extrinsic signals such as FGF regulate different stem cell states will be crucial to harvest the clinical promise of induced pluripotent and embryo-derived stem cells...

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..The combination of highly specific gene expression profiling and genome-wide ChIP analysis is a powerful means of understanding developmental pathways, even for small cell populations such as the notochord...

..asp). The clones are available as a resource to researchers worldwide to help to functionally annotate the mammalian genome and will serve as a source to test candidate loci identified by phenotype-driven mutagenesis screens...

..These adhesive differences suggest an evolving compartmentalization in multipotent NSCs during development and serve to illustrate the importance of cell-cell association for revealing cellular contribution...

..These endoderm progenitor cells maintain a stable phenotype through many passages in culture, thereby providing new tools to explore the pathways of endoderm differentiation...

..However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined...

..Targeting maternal sFlt1 levels for treatment of preeclampsia may thus be possible without affecting the proper formation of the placenta...

..Thus, the death of Brca1(5-6) mutant embryos prior to gastrulation may be due to a failure of the proliferative burst required for the development of the different germ layers...

..Therefore, the product of the cobl gene may also prove to be an important component of the genetic pathway regulating vertebrate axis formation...

..5 days post-coitum. Finally, we have genetically and physically mapped Mash2 to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2 and H19...

..This analysis demonstrates essential functions for TEK and TIE in maintaining the integrity of the mature vasculature...

..However, we have found that somitogenesis is delayed and disorganized in Notch1 mutant embryos. We propose that Notch1 normally coordinates the process of somitogenesis, and we provide a model of how this might occur...

..Together these methods will ease the access of the broader biomedical research community to the publicly available B6 ES cell resources...

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..0 and E10.0. This atlas is freely available at http://www.mouseimaging.ca/research/mouse_atlas.html and will serve as a platform to provide insight into normal and abnormal vascular development...

..This chapter will discuss the initial derivation of trophoblast stem cells from the blastocyst stage, maintenance, differentiation, flow cytometry and transfection techniques that can be used with these cells...

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..Gene-trap expression screening can thus be used to identify early endothelial-specific genes and analyze their function in mice...

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..Together, these mechanisms guide the differentiation of the first lineages of the mouse and thereby set up tissues that will be important for the first steps of embryonic body patterning...

..These results suggest that the V(0) complex has proton-pumping-independent functions in mammalian cells...

..This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure...

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..These studies provide a novel link between FGF/Erk signaling and cell survival that may be relevant to other stem and progenitor cell niches...

..HNF-3 beta is not required for the development of definitive endoderm cells, but foregut morphogenesis is severely affected in HNF-3 beta -/- embryos...

..Our results suggest the possibility that a mechanism other than DNA methylation, such as allele-specific chromatin conformation, may be involved in maintenance of parental origin-specific expression of Mash2...

..TIE is not essential, however, for vasculogenesis, the early differentiation of endothelial cells...

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..Mash-2 is the first transcription factor shown to play a critical part in the development of the mammalian trophoblast lineage...

..In addition, the forebrain truncations suggest an involvement of both genes in anterior patterning, through their overlapping expression domains in either the AVE and/or the prechordal mesoderm...

..Based on gene expression analysis, chimera studies and imprinted X-inactivation, XEN cell lines are representative of extra-embryonic endoderm and provide a new cell culture model of an early mammalian lineage...

..The early onset of the disease, predictable progression, and differences in inflammatory cell localization between the two mutants make these mice particularly useful models for inflammatory hair loss and autoimmune diseases in general...

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..This study illustrates the importance of generating different mutations at a given locus to elucidate fully the function of a particular gene during development...

..We show that such mutant embryos lack foregut and midgut endoderm. In addition, left-right asymmetry is affected in the mutant embryos...

..These results suggest that FGFR-1 transduces signals that specify mesodermal cell fates and regional patterning of the mesoderm during gastrulation...

..Such embryos, in which endogenous p120-Ras GTPase-activating protein (RasGAP), encoded by Rasa1 (also known as RasGAP), was silenced, had the same phenotype as did the previously reported Rasa1 null mutation...

..We propose a model in which the combinatorial effects of Flk1 and Tal1 act to regulate cell fate choice in early development into hematopoietic, endothelial, and smooth muscle lineages...

..Our results imply that Gli2 is required to mediate high level but not low level Shh activity and show that the development of motor neurons can occur in the absence of floor plate induction...

..Our results demonstrate conservation of the Notch pathway and its regulatory mechanisms from fly to mouse, and support a role for the murine Notch signalling pathway in the regulation of neural stem cell differentiation...

..Microarray data posted on the internet can be reanalyzed to study a range of questions...

..This, and the possibility of subsequent lineage-specific or conditional allele repair in situ, represent new genome modification strategies that can be used to investigate multiple functions of a single gene...

..Our views on chimaeras presented below definitely contain elements which grew out from this principle...

..We suggest that the Flt-1 signalling pathway may regulate normal endothelial cell-cell or cell-matrix interactions during vascular development...

..Defects specific to later specialized cell types where Pod1 is expressed, such as the podocytes, were also observed, suggesting that this transcription factor may play multiple roles in kidney morphogenesis...

..Understanding the initial developmental status of the different pluripotent lines is critical for defining starting conditions for differentiation toward therapeutically relevant cell types...

..These results show that FoxH1 functions in an activin/nodal-Smad signaling pathway that acts upstream of Foxa2 and is required specifically for patterning the APS and node in the mouse...

..Consistent with this hypothesis, the mutant mice showed abnormal foliation in the adult cerebellum, where En-2, and not En-1, is normally expressed...

..These results support a model in which separate, lineage-related EGF- and FGF-responsive neural stem cells are present in the embryonic telencephalic germinal zone...

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..These results indicate that Flk-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo...

..We propose that modulation of cytoplasmic beta-catenin levels, associated with FGF-induced downregulation of E-cadherin, provides a molecular link between FGF and Wnt signaling pathways at the streak...

..These results provide the first direct evidence for a role of mesendoderm in induction and regionalization of neural tissue in mouse...