Modulation of Ras Signaling by NF1 and CrkL in Development
Abstract
NF1 gene mutations are the genetic basis of neurofibromatosis type 1, a common genetic disorder predisposing patients to neoplasia in the peripheral nervous system and other tissues. The NF1 gene encodes a protein called neurofibromin that may negatively regulate the small G-protein Ras. Abnormal activation of Ras can cause sustained cell survival and growth in some cells (a hallmark of cancer). Aberrant Ras signaling due to a mutation in the NF1 gene is thought to contribute to the development of dermal neurofibromas and malignant peripheral nerve sheath tumors, characteristic features of neurofibromatosis type I. We have recently generated a model in which the gene encoding the adapter protein CrkL is disrupted resulting in a phenotype similar to that of NF1 disruption, including heart defects (double outlet right ventricle and ventricular septal defect), exencephaly and peripheral nerve defects. Our preliminary analysis of the CrkL mutant phenotype indicates that CrkL is essential for neural crest cells. We propose in this application to study the biological role of CrkL during development in conjunction with NF1 (Specific Aim 1) and to determine the role of the CrkL protein in regulation of Ras signaling in neural crest cells (Specific Aim 2).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA428504
Entities
People
- Akira Imamoto
Organizations
- University of Chicago