GUILLERMO C OLIVER

..A transcriptomic analysis of early human organogenesis reveals the molecular signature of these processes and provides a valuable resource for identifying and comparing crucial regulators of mammalian embryogenesis...

..Understanding these basic mechanisms of lymphatic development will improve our ability to diagnose, prevent, and ideally treat lymphatic disorders...

....

....

..This knowledge, in turn, should lead to the development of better diagnostic methods and treatments of lymphatic disorders and tumor metastasis...

..Therefore, LECs are one of the few differentiated cell types that require constant expression of a certain gene to maintain their phenotypic identity...

..We conclude that the mammalian lymphatic system has a solely venous origin...

..In addition, we show that the direct interaction between nuclear hormone receptors and Prox1 is also necessary for the maintenance of Prox1 expression during early stages of LEC specification and differentiation...

..On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype...

..Prox1 thus appears to be an essential component of a genetic program destined to produce the cellular complexity of the mammalian pancreas...

..Recent discoveries have impacted our understanding of the embryonic origins of arterial, venous and lymphatic endothelial cells and the signals that mediate their navigation into mature, functional circulatory systems...

..Thus, Prox1 activity is both necessary and sufficient for progenitor-cell proliferation and cell-fate determination in the vertebrate retina...

..In adulthood, Prox1 expression remains only in the hippocampus and cerebellum. These complex patterns of expression suggest that Prox1 activity is differentially required during brain development and adulthood...

..This finding indicates that Prox1 is one of the earliest specific markers of this commonly fated region of the mammalian endoderm...

..Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease...

..5, Sox9, and Gremlin) also appear to be required for the formation of this structure in mammals. Thus, we propose that Six2 activity regulates this gene network during the genesis of the pyloric sphincter in the mouse...

..In this review, we summarize the functional roles of the lymphatic vasculature in health and disease...

..These results identify Six3 as a direct regulator of Shh expression and reveal a crossregulatory loop between Shh and Six3 in the ventral forebrain...

..These results provide insight into the mechanisms that establish anteroposterior identity in the developing mammalian brain...

..Our results show that Six3OS expression overlaps extensively with that of Six3 and is not altered in Six3-null embryos...

..We conclude that Six3 directly activates Pax6 and probably also Sox2 in the PLE and regulates cell autonomously the earliest stages of mammalian lens induction...

..We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud...

..These specific alterations were not seen when the mutated form of Six3 cDNA was used in similar experimental approaches, indicating that Six3 interaction with Groucho proteins plays an essential role in vertebrate eye development...

..Moreover, Six3 with HPE-causing alterations failed to bind and activate SBE2. These data suggest a direct link between Six3 and Shh regulation during normal forebrain development and in the pathogenesis of HPE...

..Furthermore, these results support the hypothesis that a Wnt signal gradient specifies posterior fates in the anterior neural plate...

....

..Thus, they will enhance our understanding of eye-related birth defects. ..

....

..abstract_text> ..

....

....

..abstract_text> ..

..To this end, we propose to continue using Six3 as an entry point to better characterize its functional role in the development of different brain structures and retina differentiation and lamination. ..

....

..abstract_text> ..

..These experiments will further define the mechanisms and pathways involved in vertebrate cell differentiation, and should help to understand the role of Prox1 during this process. ..

..To this end, we propose to continue using Six3 as an entry point to better characterize its functional role in the development of different brain structures and retina differentiation and lamination. ..