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  • DKFZ Publication Database  (2)
  • CELLS  (2)
  • Cell Proliferation
  • 1
    Abstract: OBJECTIVE: To characterize the role of a vascular-expressed class 3 semaphorin (semaphorin 3G [Sema3G]). METHODS AND RESULTS: Semaphorins have been identified as axon guidance molecules. Yet, they have more recently also been characterized as attractive and repulsive regulators of angiogenesis. Through a transcriptomic screen, we identified Sema3G as a molecule of angiogenic endothelial cells. Sema3G-deficient mice are viable and exhibit no overt vascular phenotype. Yet, LacZ expression in the Sema3G locus revealed intense arterial vascular staining in the angiogenic vasculature, starting at E9.5, which was detectable throughout adolescence and downregulated in adult vasculature. Sema3G is expressed as a full-length 100-kDa secreted molecule that is processed by furin proteases to yield 95- and a 65-kDa Sema domain-containing subunits. Full-length Sema3G binds to NP2, whereas processed Sema3G binds to NP1 and NP2. Expression profiling and cellular experiments identified autocrine effects of Sema3G on endothelial cells and paracrine effects on smooth muscle cells. CONCLUSIONS: Although the mouse knockout phenotype suggests compensatory mechanisms, the experiments identify Sema3G as a primarily endothelial cell-expressed class 3 semaphorin that controls endothelial and smooth muscle cell functions in autocrine and paracrine manners, respectively.
    Type of Publication: Journal article published
    PubMed ID: 20947821
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  • 2
    Keywords: ANGIOGENESIS ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; BLOOD ; CELL ; ENDOTHELIAL GROWTH-FACTOR ; Germany ; GENE ; transcription ; DIFFERENTIATION ; EPITHELIA ; TRANSCRIPTION FACTOR ; INJECTION ; BIOLOGY ; MOUSE ; DISRUPTION ; inactivation ; COMPLEMENTATION ; EPITHELIAL-CELLS ; STRATEGIES ; RECEPTORS ; INSIGHTS ; VESSELS ; nude mice ; SUBSETS ; ARCHITECTURE ; LETHALITY ; MORPHOGENESIS ; targeting ; molecular ; thymus ; MOLECULAR-BASIS ; SUBSET ; ALLELE ; BLOOD-VESSELS ; gene targeting ; mesenchyme ; development ; ALLELES ; EPITHELIUM ; function ; branching ; nude mouse blastocyst complementation ; thymus development ; VASCULAR DEVELOPMENT ; vascular endothelial growth factor
    Abstract: The thymus harbors an organ-typical dense network of branching and anastomosing blood vessels. To address the molecular basis for morphogenesis of this thymus-specific vascular pattern, we have inactivated a key vascular growth factor, VEGF-A, in thymus epithelial cells (TECs). Both Vegf-A alleles were deleted in TECs by a complementation strategy termed nude mouse [mutated in the transcription factor Foxn1 (forkhead box N1)] blastocyst complementation. Injection of Foxn1(+/+) ES cells into Foxn1(nu/nu) blastocysts reconstituted a functional thymus. By dissecting thymus stromal cell subsets, we have defined, in addition to medullary TECs (mTECs) and cortical TECs (cTECs), another prominent stromal cell subset designated cortical mesenchymal cells (cMes). In chimeric thymi, mTECs and cTECs but not cMes were exclusively ES cell-derived. According to this distinct origin, the Vegf-A gene was deleted in mTECs and cTECs, whereas cMes still expressed Vegf-A. This genetic mosaic was associated with hypovascularization and disruption of the organ-typical network of vascular arcades. Thus, vascular growth factor production by TECs is required for normal thymus vascular architecture. These experiments provide insights into Foxn1-dependent and Foxn1-independent stromal cell development and demonstrate the value of this chimeric approach to analyzing gene function in thymus epithelium
    Type of Publication: Journal article published
    PubMed ID: 16027358
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