Regulating heart development: the role of Nf1.
Neurofibromatosis type 1 (NF1) is one of the most common human genetic disorders and is associated with significant morbidity and mortality. The gene responsible for this disorder, NF1, encodes neurofibromin, which can function to down-regulate ras activity. Mutations that inactivate NF7 result in elevated levels of ras signaling and increased cell proliferation in some tissues. NF7 functions as a tumor suppressor gene; patients inherit one mutated copy and are believed to acquire a "second hit" in tissues that go on to form benign or malignant tumors. NF7 is expressed widely, yet certain tissues are more susceptible to growth dysregulation in NF1 patients. Cardiovascular defects also contribute to NF1, though the cause remains unclear. In a recent study, we used tissue-specific gene inactivation in mice to study the role of neurofibromin in heart development. A further understanding of neurofibromin function will help to elucidate the pathophysiology of NF1 and will also lead to a better understanding of cell cycle regulation and ras pathways in specific cell types. Finally, we comment on how similar genetic strategies can be used in mice to study the role of additional signaling pathways involved in heart development.
Gitler
Aaron D
AD
Department of Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
Epstein
Jonathan A
JA
D000818:Animals; D016514:Genes, Neurofibromatosis 1 / Q000502:physiology*; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology*; D006801:Humans; D051379:Mice; D009456:Neurofibromatosis 1 / Q000235:genetics; D015398:Signal Transduction