College
Morsani College of Medicine
Mentor Information
Saulius Sumanas
Description
Vascular tubulogenesis is the process by which endothelial cells organize into hollow tubes that permit blood flow. Despite its importance, the molecular mechanisms governing tubulogenesis remain poorly understood, and defects in this process underlie a range of diseases.
Src homology 2 domain-containing E (She) was originally characterized as an endothelial-enriched adaptor protein that functions downstream of the ETS transcription factor Etv2 / Etsrp in zebrafish embryos. She’s protein sequence was also previously determined to be evolutionarily conserved between different vertebrates, including Homo sapiens. Even so, its role and biological function remained unknown. This study describes the discovery of she’s function during vascular tubulogenesis. Using a zebrafish she mutant line created by the Sumanas Lab, it was determined that She is essential for regulation of vascular lumen size during early development. Loss of she function was determined to produce two distinct vascular phenotypes: enlargement of the dorsal aorta (DA) at early stages and high rates of DA collapse accompanied by circulatory failure at later stages of development. Around the 8dpf mark, mutants were found to not survive.
DA enlargement in she mutants was found to result from increased endothelial cell proliferation. DA collapse, by contrast, was linked to decreased vessel stiffness, which was found to result from altered activity of mural cells and faulty deposition of extracellular matrix proteins. Reduced vessel stiffness increases susceptibility to structural failure and circulatory collapse. These findings position She as a key regulator of vascular tubulogenesis.
Role of She in Vascular Tubulogenesis
Vascular tubulogenesis is the process by which endothelial cells organize into hollow tubes that permit blood flow. Despite its importance, the molecular mechanisms governing tubulogenesis remain poorly understood, and defects in this process underlie a range of diseases.
Src homology 2 domain-containing E (She) was originally characterized as an endothelial-enriched adaptor protein that functions downstream of the ETS transcription factor Etv2 / Etsrp in zebrafish embryos. She’s protein sequence was also previously determined to be evolutionarily conserved between different vertebrates, including Homo sapiens. Even so, its role and biological function remained unknown. This study describes the discovery of she’s function during vascular tubulogenesis. Using a zebrafish she mutant line created by the Sumanas Lab, it was determined that She is essential for regulation of vascular lumen size during early development. Loss of she function was determined to produce two distinct vascular phenotypes: enlargement of the dorsal aorta (DA) at early stages and high rates of DA collapse accompanied by circulatory failure at later stages of development. Around the 8dpf mark, mutants were found to not survive.
DA enlargement in she mutants was found to result from increased endothelial cell proliferation. DA collapse, by contrast, was linked to decreased vessel stiffness, which was found to result from altered activity of mural cells and faulty deposition of extracellular matrix proteins. Reduced vessel stiffness increases susceptibility to structural failure and circulatory collapse. These findings position She as a key regulator of vascular tubulogenesis.
