In the development of Schwann cell lineage, multipotent neural crest cells give rise to Schwann cell precursors, which in turn differentiate into Schwann cells.
The aim of this project ist to analyse the involvement of the putative gene regulatory protein Dlw-l, and the tyrosine kinase receptor Sek-l, in Schwann cell development. Different observations raise the possibility that these two genes might be involved in the Schwann cell differentiation. First, Dlx1 is a member of a novel family of vertebrate genes sharing a homeodomain sequence similar to that found in the Drosophila Distal-less gene. During mouse development, Dlx-l is detected in different neural crest cell derivatives and is likely to be expressed by Schwann cell precursors. Second, Sek-1 belongs to the Eph subfamily of receptor tyrosine kinases.
During mouse development, Sek-1 is co-expressed with Krox-2O which is expressed in Schwann cells before the onset of myelination.
The aim of the present project is: 1) To study the expression patterns of Dlx-l and Sek-l in the Schwann cell lineage, and to relate them to known developmental transition points. 2) To investigate the role of different growth factors, known to be involved in Schwann cell differentiation, in the regulation of DIx-1 and Sek-l expression. 3) To interfere with Dlw-l and Sek-1 expression using antisense technologies in order to study the direct involvement of these two genes in different steps of Schwann cell generation and Schwann cell differentiation. 4) To inhibit the interaction between Sek-l and a putative ligand by means of a soluble form of Sek-1 receptor.