Notch signaling controls multiple steps of pancreatic differentiation

LC Murtaugh, BZ Stanger, KM Kwan… - Proceedings of the …, 2003 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
Multiple cell types of the pancreas appear asynchronously during embryogenesis, which
requires that pancreatic progenitor cell potential changes over time. Loss-of-function studies
have shown that Notch signaling modulates the differentiation of these progenitors, but it
remains unclear how and when the Notch pathway acts. We established a modular
transgenic system to heritably activate mouse Notch1 in multiple types of progenitors and
differentiated cells. We find that misexpression of activated Notch in Pdx1-expressing …
Multiple cell types of the pancreas appear asynchronously during embryogenesis, which requires that pancreatic progenitor cell potential changes over time. Loss-of-function studies have shown that Notch signaling modulates the differentiation of these progenitors, but it remains unclear how and when the Notch pathway acts. We established a modular transgenic system to heritably activate mouse Notch1 in multiple types of progenitors and differentiated cells. We find that misexpression of activated Notch in Pdx1-expressing progenitor cells prevents differentiation of both exocrine and endocrine lineages. Progenitors remain trapped in an undifferentiated state even if Notch activation occurs long after the pancreas has been specified. Furthermore, endocrine differentiation is associated with escape from this activity, because Ngn3-expressing endocrine precursors are susceptible to Notch inhibition, whereas fully differentiated endocrine cells are resistant.
National Acad Sciences