EMBRYONIC EXPRESSION OF THE MYELIN BASIC-PROTEIN GENE - IDENTIFICATION OF A PROMOTER REGION THAT TARGETS TRANSGENE EXPRESSION TO PIONEER NEURONS

The myelin basic protein (MBP) gene produces two families of structura lly related proteins from three different promoters-the golli products , generated from the most upstream promoter, and the MBPs, produced fr om the two downstream promoters. In this report we describe the expres sion of golli proteins within some of the earliest neuronal population s of the brain, including Cajal-Retzius cells and preplate neurons of the forebrain, representing a new marker for these cells. To identify elements responsible for neuronal expression of the golli products, we generated transgenic animals from constructs containing different por tions of the upstream promoter. A construct containing 1.1 kb immediat ely upstream of the golli transcription start site targeted expression of beta-galactosidase to preplate neurons and a subset of Cajal-Retzi us cells in transgenic mice-the first reported genetic element to targ et expression to these pioneer cortical populations. Although expressi on in Cajal-Retzius cells declined with embryonic development, preplat e cells continued to express the transgene after arriving at their fin al destination in the subplate. Interestingly, expression persisted in subplate neurons found within a distinct layer between the white matt er and cortical layer VI well into postnatal life. Birth dating studie s with bromodeoxyuridine indicated that these neurons were born betwee n E10.5 and E12.5. Thus, the transgene marked subplate neurons from th eir birth, providing a fate marker for these cells. This work suggests a role for the MBP gene in the early developing brain long before mye lination and especially in the pioneer cortical neurons important in t he formation of the cortical layers.