Aim: 

Cell surface glycoproteins play a relevant role in nervous tissue morphogenesis and function. Here we use transgenic mice models leading to misexpression of such molecules to explore the significance of their regulated expression profile.

Methods: 

TAG/F3 transgenic mice, undergoing early overexpression of the axonal adhesive F3/Contactin under control of the regulatory region of the gene encoding the close relative Transient Axonal Glycoprotein (TAG-1) have been used. In these mice the developmental profile of ventricular zone precursors has been studied both in vivo and in vitro through the expression of cell-specific markers, allowing us to follow the profile of neuronal and glial precursors. The expression of Notch pathway components, known to play a critical role in the balance of precursor versus differentiating elements has been also explored.

Results: 

F3/Contactin overexpression was found to result in changes of ventricular zone precursor proliferation and differentiation. In particular an increased length of the S phase was observed, consistent with a reduced tendency of precursors to exit the cell cycle. Differentiation of neuronal precursors was also delayed by F3/Contactin overexpression, while opposte effects were observed on glial precursors. The concomitant and opposite effects on neuronal and glial precursor differentiation, and on precursor proliferation suggested the involvement of the Notch pathway, which could be confirmed by a sharp upregulation in transgenic mice of the Notch intracellular domain (NICD) and of the Hes-1 transcription factor.

Conclusions: 

The reported data indicate that axonal adhesive glycoproteins may control neural development by activating pathways of key relevance in developmental control as is the Notch pathway.