Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4

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Notch signalling relies on binding of a ligand to a Notch receptor, both residing on the surfaces of neighbouring cells. This interaction forwards a signal into the receptor-expressing cell, this way coordinating cells in many biological processes such as the segmentation of the axial skeleton. Mammals possess four Notch-activating ligands–including DLL1 and DLL4 -expressed in diverse, partially overlapping regions. Whether the different ligands trigger quantitatively or qualitatively distinct Notch responses is largely unknown. In order to directly compare both ligands we generated transgenic mice that express DLL1 or DLL4 in identical patterns. These mice uncover that only DLL1 but not DLL4 can mediate regular segmentation of the embryo. In experiments with cultured cells expressing either ligand and Notch, we found that the functional difference observed is unlikely to depend on differences in the activation of Notch. Rather, the unsuspected but strong difference between both ligands in cis-inhibition, i.e. repression of Notch by a ligand expressed in the same cell as the receptor, a process described in the fruitfly but not in mammals and not for DLL4 provides a possible explanation for the divergence in tissues that coexpress ligand and receptor.

Vyšlo v časopise: Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005328
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005328

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