First published online January 10, 2007
Development 134, 305e (2007)
© The Company of Biologists Limited
Notches marked up
The ligand-activated Notch receptor undergoes proteolytic cleavages, which
release an intracellular fragment that activates target genes. Notch
signalling regulates many cell fate decisions, but determining where and when
it is activated has proven problematic. Now, on
p. 535, Raphael Kopan
and colleagues reveal a novel genetic approach in mice to locate Notch
activation during development. Using an N1IP-CRE allele, in which
the Notch1 intracellular fragment is replaced by Cre, they have mapped Notch
activity via ß-galactosidase expression. This approach is particularly
novel as this transgene marks descendents of a progenitor cell. Using this
technique, they identify novel roles for Notch1 signalling in the heart,
vasculature, retina and stem cell compartments of self-renewing epithelia.
Interestingly, high levels of Notch1 activation do not always correlate with
it having an essential role, as is revealed for intestinal stem cells.
Together, these findings provide new insights into Notch activation and
subsequent cell fate choice. Similar studies on the other Notch receptors in
the mouse should provide further new information.
Related articles in Development:
- Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE
- Marc Vooijs, Chin-Tong Ong, Brandon Hadland, Stacey Huppert, Zhenyi Liu, Jeroen Korving, Maaike van den Born, Thaddeus Stappenbeck, Yumei Wu, Hans Clevers, and Raphael Kopan
Development 2007 134: 535-544.
[Abstract]
[Full Text]
