TY - JOUR
T1 - The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in Drosophila
AU - Bray, Sarah J.
AU - Takada, Shuji
AU - Harrison, Emma
AU - Shen, Shing Chuan
AU - Ferguson-Smith, Anne C.
PY - 2008
Y1 - 2008
N2 - Background. Mammalian Delta-like 1 (Dlk-1) protein shares homology with Notch ligands but lacks a critical receptor-binding domain. Thus it is unclear whether it is able to interact with Notch in vivo. Unlike mammals, Drosophila have a single Notch receptor allowing a simple in vivo assay for mammalian Dlk1 function. Results. Here we show that membrane-bound DLK1 can regulate Notch leading to altered cellular distribution of Notch itself and inhibiting expression of Notch target genes. The resulting adult phenotypes are indicative of reduced Notch function and are enhanced by Notch mutations, confirming that DLK1 action is antagonistic. In addition, cells expressing an alternative Dlk1 isoform exhibit alterations in cell size, functions previously not attributed to Notch suggesting that DLK1 might also act via an alternative target. Conclusion. Our results demonstrate that DLK1 can regulate the Notch receptor despite its atypical structure.
AB - Background. Mammalian Delta-like 1 (Dlk-1) protein shares homology with Notch ligands but lacks a critical receptor-binding domain. Thus it is unclear whether it is able to interact with Notch in vivo. Unlike mammals, Drosophila have a single Notch receptor allowing a simple in vivo assay for mammalian Dlk1 function. Results. Here we show that membrane-bound DLK1 can regulate Notch leading to altered cellular distribution of Notch itself and inhibiting expression of Notch target genes. The resulting adult phenotypes are indicative of reduced Notch function and are enhanced by Notch mutations, confirming that DLK1 action is antagonistic. In addition, cells expressing an alternative Dlk1 isoform exhibit alterations in cell size, functions previously not attributed to Notch suggesting that DLK1 might also act via an alternative target. Conclusion. Our results demonstrate that DLK1 can regulate the Notch receptor despite its atypical structure.
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U2 - 10.1186/1471-213X-8-11
DO - 10.1186/1471-213X-8-11
M3 - Article
C2 - 18237417
AN - SCOPUS:40949124822
SN - 1471-213X
VL - 8
JO - BMC Developmental Biology
JF - BMC Developmental Biology
M1 - 11
ER -