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yin198716新蟲 (正式寫手)
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Lateral Inhibition Selects the Tip Cell The specification of ECs into tip and stalk cells is controlled by the Notch pathway . Analysis of Notch signaling revealed high Notch activity in stalk cells but low levels of Notch signaling in tip cells. Conversely, tip cells express higher levels of the Notch ligand DLL4. During development or in tumors, blockade of Notch or DLL4 increases filopodia and sprouting as a consequence of excessive tip cell formation. Although ECs express several Notch receptors, Notch1 is critical for suppressing tip cell behavior in stalk cells. The hypersprouting phenotype and excessive number of tip cells following Notch inhibition indicate that the tip cell phenotype is the default endothelial response to proangiogenic signals. In contrast to DLL4, the Notch ligand JAGGED1 (JAG1) is expressed primarily by stalk cells. However, JAG1 poorly activates Notch1, as modification of Notch by FRINGE glycosyltransferases favors activation by DLL4 . Given that some DLL4 protein is detectable in stalk cells, JAG1 helps to maintain differential Notch activity by antagonizing DLL4 that signals back to tip cells. |
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