- To analyse in vivo and in vitro the role of homeogenes in the transcriptional control of CAMs.

- To understand the mode of transduction of NCAM and other adhesion receptors, focusing on the FGF receptor.

- To develop new therapeutical approaches based on the use of polypeptides derived from soluble CAMs endowed with signalling properties and of homeodomain peptides that translocate through the plasma membrane.

The molecular and cellular basis of the regulation of adhesion molecules (NCAM, TAG-1, APP and F3) by developmental genes, homeogenes in particular, will be analysed. This part of the study will include promoter analysis in vitro (sequencing), ex vivo (transfection), and in vivo (transgenesis). Mice bearing null mutations for some transcription factors will be prepared and the consequence of the mutations on adhesion molecule (or promoter) expression will be followed. The role of the FGF receptor FGF-R1 in signalling the effects of adhesion molecules such as NCAM and L1 will be analysed in vitro and in vivo. In the latter case experimental models allowing for the study of neuronal plasticity in the adult, for example morphological modifications that accompany lactation, will be used. Mice carrying null mutations for NCAM or dominant negative forms of neuronal FGF-R1 will be used to assess the importance of these molecules in plasticity. In view of the increasing evidence that developmental genes and CAMs are involved in several pathologies, these studies, in addition to their basic aspects, have the ambition to permit a better understanding of several genetic and acquired diseases at the molecular and cellular levels. They also have the potential to lead to the development of new therapeutic strategies for neuroprotection and nerve regeneration based on the use of soluble CAMs or CAM fragments and on the capability of homeopeptides to serve as vectors for the intracellular and nuclear addressing of pharmacological agents.