*Vacca A, *Di Marcotullio L. hanno ugualmente contribuito a questo lavoro Thymic epithelial cell component originates from cranial neural crest as well as from endoderm and ectoderm of the third pharyngeal pouch and branchial cleft, Epidermal growth factor (EGF) has been previously shown to play a crucial role in directing thymic epithelial cells toward a neural-oriented cell fate. To identify genes that are involved in the EGF-induced neurotypic differentiation of the thymic stroma derived TC-1S cell line, we studied EGF treated and untreated cells by RNA fingerprinting PCR-based differential screening. We obtained 23 distinct sequences including 18 known genes and 5 sequences previously unreported, which are currently under characterization. Here, we describe the involvement of one of the isolated genes, the thrombospondin-l, as a mediator of the neurotypic differentiation induced by EGF in TC-1S cells. We show that thrombospondin-l mRNA and protein levels are increased by EGF. More over, exogenous thrombospondin-l is able to enhance the outgrowth of neurite like processes as well as the expression of neurofilaments and neural cell adhesion molecule in TC-1S cells. These observations suggest that the up-regulation of thrombospondin-l synthesis induced by EGF contributes to the differentiation choice of thymic epithelial cells toward a neural fate, reminiscent of their neural crest origin.