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669522 
Technical Report 
Cell Motility and Invasiveness of Neurofibromin-Deficient Neural Crest Cells and Malignant Triton Tumor Lines 
Vogel, KS 
2001 
Texas University Medical School 
San Antonio, TX 
22 
Annual rept. 1 Oct 2000-30 Sep 2001. Our purpose is to examine the role of the NF1 gene product, neurofibromin, in modulating the migratory and invasive properties of neural crest cells (NCC) and neural crest-derived sarcoma cells. As a negative regulator of Ras signaling, neurofibromin may influence the responses of NC- derived cells to growth factors and extracellular matrix (ECM) molecules that affect motility. We use embryonic NCC and NC-derived sarcoma lines isolated from cisNf1 ;p53 mice to compare integrin ECM receptor expression patterns, ECM adhesion preferences, migration on ECM substrata, invasion through ECM barriers, and dispersal along NCC pathways in vivo for wild-type and neurofibromin- deficient cells. In the five months since funding was transferred to UTHSCSA, we have developed dissection and culture methods for embryonic mouse branchial arch neural crest cells, and determined that Nfl-/- maxillary and mandibular NCC are more invasive through fibronectin and laminin. In addition, we have correlated MTT phenotype with invasive potential, and characterized effects of growth factors on MTT sarcoma cell invasiveness. Our studies address two important questions: (1) what molecules control the migration and localization of NCC in the embryo. (2) which growth factor signaling pathways affect the invasiveness of NC-derived sarcoma cells.