DIFFERENTIAL PATTERNS OF SEMAPHORIN EXPRESSION IN THE DEVELOPING RAT-BRAIN

Semaphorins are a large family of cell-surface and secreted proteins t hat have been shown to function as chemorepellents or inhibitors of gr owth cones of peripheral neurons, yet little is known about their role in patterning central pathways. In order to examine whether semaphori ns may be involved in guiding the formation of the reciprocal thalamoc ortical connections in the rat, we have analysed the spatial and tempo ral expression of five recently identified rodent semaphorins (semB, C , D, F and G) using in situ hybridization. Transcripts of all five gen es were present throughout the period examined (E15-P7) and displayed highly specific spatiotemporal distributions. We have based our discus sion of putative semaphorin effects on their known functions as chemor epellents and found their spatiotemporal expression patterns compatibl e with such a role in several developmental events. Specifically, sema phorins are in the position to: (i) prevent neurite extension into the ventricular neuroepithelium throughout the brain; (ii) confer non-per missive properties to the embryonic cortical plate, hence regulating t he radial invasion of corticopetal afferents; (iii) confine axonal ext ension to the intermediate zone and subplate; (iv) maintain the fascic ulated state of thalamocortical and corticothalamic axons, and prevent them from branching while they grow through the striatum; and (v) res trict the terminal arborizations of thalamic afferents to layer IV. Th e evidence that different semaphorin genes are often co-expressed furt her suggests that the various molecules might interact in synergistic ways. Taken together, our results support the hypothesis that semaphor ins could act as guidance signals in the development of the thalamocor tical projections and suggest that innervation specificity is achieved through the combined action of multiple guidance cues. Furthermore, t hese data provide a basis for the design of functional assays and the study of mice carrying knockouts in specific semaphorin genes.