LOCALIZATION OF PLEIOTROPHIN AND ITS MESSENGER-RNA IN SUBPOPULATIONS OF NEURONS AND THEIR CORRESPONDING AXONAL TRACTS SUGGESTS IMPORTANT ROLES IN NEURAL-GLIAL INTERACTIONS DURING DEVELOPMENT AND IN MATURITY

Trophic factors are being increasingly recognized as important contrib utors to growth, differentiation, and maintenance of viability within the mammalian nervous system during development. Pleiotrophin (PTN) is a secreted 18-kDa heparin binding protein that stimulates mitogenesis and angiogenesis and neurite and glial process outgrowth guidance act ivities in vitro. We localized the sites and time course of expression of the Ptn gene and its protein product in developing and adult mouse nervous system. Expression of the Ptn gene was first observed at embr yo day 8.5 (E8.5). At E12.5, transcripts of the Ptn gene were localize d in developing neuroepithelium at sites of active cell division in th e spinal cord and brain. At E15.5, transcripts were found in the somat a of some but not all neurons and glia whereas in the adult its patter n of expression was nearly exclusively restricted to the brain. The PT N protein was found almost entirely in association with the axonal tra cts during development and in adults. Furthermore, as opposed to the f inding of PTN in both central and peripheral nervous systems during de velopment, PTN was not expressed beyond the exit where axonal tracts b ecome the peripheral nervous system in adults. At all sites and times examined, the somata that contained Ptn transcripts corresponded with the axonal tracts that contained the PTN protein. The results establis h that Ptn is expressed in early development at sites of active mitoge nesis in developing neuroepithelium and later in both glial cells and neurons at sites of neuronal and glial process formation in developing axonal tracts. The findings establish a correspondence in the localiz ation of PTN within the nervous system at sites of normal developmenta l processes that correlate with the functional activities of PTN previ ously described in vitro. (C) 1996 John Wiley & Sons, Inc.