Early induction of T alpha 1 alpha-tubulin transcription in neurons of thedeveloping nervous system

In this report, we have examined the relationship between the onset of neur onal gene transcription and neuronal development by characterizing expressi on of the early panneuronal T alpha 1 alpha-tubulin promoter in developing neurons. In the peripheral nervous system, detectable expression of a beta- galactosidase transgene driven by the T alpha 1 promoter (T alpha 1:nlacZ) was coincident with neuronal birth dates, with the exception of sympathetic neuroblasts, which expressed the transgene prior to terminal mitosis. Simi larly, in the central nervous system, the onset of beta-galactosidase expre ssion was coincident with neuronal birth dates in most identifiable populat ions of central neurons. A small subpopulation of transgene-positive cells localized to ventricular zones, but the vast majority was observed in locat ions consistent with their identification as migrating and/or differentiati ng neurons. To determine more precisely the temporal relationship between t ransgene expression and terminal mitosis, we analyzed cultures of cortical progenitors that become postmitotic neurons in vitro. When initially plated , the vast majority of cells consisted of dividing, nestin-positive progeni tors. Neurons differentiated from these progenitors as early as 1 day in vi tro, as indicated by immunostaining for beta III-tubulin, a neuron-specific tubulin isotype that is turned on shortly after terminal mitosis. Double-l abeling studies showed that T alpha 1:nlacZ expression was detectable in th e same cells and at approximately the same time as was beta III-tubulin, in dicating that detectable transcription of the T alpha 1 alpha-tubulin promo ter commences at the time of terminal mitosis, at least in culture. This pr omoter, therefore, provides a valuable tool for genetic manipulation of ear ly developing neurons in transgenic mice. (C) 1999 Wiley-Liss, Inc.