Hey, there's a hole in my heart.

摘要

Mutations in genes encoding the developmental regulators Notch cause an amalgam of defects such that the many roles of this signaling receptor cannot be teased apart by studying the global loss of Notch alone. Instead more subtle and elegant genetic manipulations are called for to discern the multiple roles of Notch. In the current issue of Circulation Research Fischer et al describe a major step toward the understanding of Notch signaling not through the manipulation of the receptor itself, but by studying the loss of two of its downstream effectors. Alone, neither the loss of function of Heyl nor HeyL appear as necessary contributors to proper heart development. Loss of both Heyl and HeyL however, leads to atrioventricular (AV) dysplasia and membranous ventricular septal defects during cardiogenesis. These phenotypes mimic common congenital heart defects found in the human population and demonstrate a more accurate mouse model that can be used in studying human disease and genetic anomalies.