Courtney K Domigan1, M Luisa Iruela-Arispe. 1. Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, Los Angeles, California, USA.
Abstract
PURPOSE OF REVIEW: This review offers a concise summary of the most recent experimental advances in vascular development using the mouse as a model organism. RECENT FINDINGS: Recent mouse studies have revealed a spread of phenotypic diversity between endothelia of distinct developmental origins and organs. For example, expression of unique transcription factors distinguishes hemogenic from nonhemogenic endothelium within the same vessel. Vasculature of the brain is particularly susceptible to endothelial malformations due to combinatorial germline and somatic mutations; surprisingly these mutations can afflict the endothelium by either cell autonomous or paracrine effects. Mutant mice have been used to understand how multiple signaling pathways integrate and refine cellular responses. In particular, we learned how VEGFR3 regulates Notch signaling and EphrinB2 coordinates VEGFR2 responses. The regulation of Prox1 by miR181 highlighted the contribution of microRNAs in the induction of lymphatic endothelium. Information gained on heterotypic interactions has further clarified the influence of blood vessels on the morphogenesis of parenchyma and contributed to our understanding of organ-specific endothelial differentiation. Finally, mouse models have uncovered endothelial cell polarity as a keystone for successful vascular lumenization. SUMMARY: Our understanding of the process of vascular development has gained significant refinement in the last two years and has clarified the origin of several disorders rooted in development.
PURPOSE OF REVIEW: This review offers a concise summary of the most recent experimental advances in vascular development using the mouse as a model organism. RECENT FINDINGS: Recent mouse studies have revealed a spread of phenotypic diversity between endothelia of distinct developmental origins and organs. For example, expression of unique transcription factors distinguishes hemogenic from nonhemogenic endothelium within the same vessel. Vasculature of the brain is particularly susceptible to endothelial malformations due to combinatorial germline and somatic mutations; surprisingly these mutations can afflict the endothelium by either cell autonomous or paracrine effects. Mutant mice have been used to understand how multiple signaling pathways integrate and refine cellular responses. In particular, we learned how VEGFR3 regulates Notch signaling and EphrinB2 coordinates VEGFR2 responses. The regulation of Prox1 by miR181 highlighted the contribution of microRNAs in the induction of lymphatic endothelium. Information gained on heterotypic interactions has further clarified the influence of blood vessels on the morphogenesis of parenchyma and contributed to our understanding of organ-specific endothelial differentiation. Finally, mouse models have uncovered endothelial cell polarity as a keystone for successful vascular lumenization. SUMMARY: Our understanding of the process of vascular development has gained significant refinement in the last two years and has clarified the origin of several disorders rooted in development.
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