Perspectives on the autocrine and paracrine functions of trans-activating factors

It is a more and more widespread observation that growth factors can, on occasion, be found within nuclei where they may serve as trans-activating factors. This dual action raises the possibility that, on their side, trans-activating factors might be secreted and act both at the membrane and at the nuclear level of target cells. At the same time it has now been clearly demonstrated that the classical growth factors bFGF and TGF-b are good in vitro mesodermal inducers and may have in vivo counterparts. Neural inducers, unfortunately, remain much more elusive even though the phenomenon of neural induction was described almost 60 years ago. Here, we present a short review on the development of the nervous system in which we focus on the importance of homeobox proteins in inductive phenomena. We follow on to propose that some trans-activating factors belonging to the homeoprotein family may have paracrine and autocrine functions and might thus participate directly in neural induction. This highly hypothetical proposal is based on evidence from the literature and on experiments carried out in our laboratory showing that the antennapedia homeobox peptide (pAntp) added to neurons in culture is internalised by these cells, conveyed to their nuclei and provokes their morphological differentiation.