Abstract
The transcriptional repressors Hey1 and Hey2 are primary target genes of Notch signaling in the cardiovascular system and induction of Hey gene expression is often interpreted as activation of Notch signaling. Here we report that treatment of primary human endothelial cells with serum or fresh growth medium led to a strong wave of Hey1 and Hey2 transcription lasting for approximately three hours. Transcription of other Notch target genes (Hes1, Hes5, ephrinB2, Dll4) was however not induced by serum in endothelial cells. Gamma secretase inhibition or expression of dominant-negative MAML1 did not prevent the induction of Hey genes indicating that canonical Notch signaling is dispensable. Pretreatment with soluble BMP receptor Alk1, but not Alk3, abolished Hey gene induction by serum. Consequently, the Alk1 ligand BMP9 stimulated Hey gene induction in endothelial cells. Several other cell types however did not show such a strong BMP signaling and consequently only a very mild induction of Hey genes. Taken together, the experiments revealed that bone morphogenic proteins within the serum of cell culture medium are potent inducers of endothelial Hey1 and Hey2 gene expression within the first few hours after medium change.
Highlights
Hes and Hey genes are the mammalian orthologes of hairy and enhancer-of-split genes in Drosophila.[1]
Induction of Hey1 and Hey2 transcription is often considered as readout for activation of Notch signaling in endothelial cells
We found that in particular endothelial cells react with a single wave of strong Hey1 and Hey2 expression to fresh serum
Summary
Hes and Hey genes are the mammalian orthologes of hairy and enhancer-of-split genes in Drosophila.[1] They encode basic helix-loop-helix (bHLH) transcription factors that control expression of numerous loci in the human genome.[2] Both gene families are well known as the primary effector molecules of Notch signaling,[3] and both act predominantly as transcriptional repressors.[4]. The Delta-Notch cascade is a highly conserved and highly versatile signaling system that directs a multitude of binary and inductive cell fate decisions during development. Notch receptors (Notch1-Notch4) become activated upon binding of Delta-like or Jagged ligands
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
