Neurogenesis in Tα-1 tubulin transgenic mice during development and after injury

T alpha-1 tubulin promoter-driven EYFP expression is seen in murine neurons born as early as E9.5. Double labeling with markers for stein cells (Sox 1, Sox 2, nestin), glial progenitors (S100 beta, NG2, Olig2), and neuronal progenitors (doublecortin, beta III-tubulin, PSA-NCAM) show that T alpha-1 tubulin expression is limited to early born neurons. BrdU uptake and double labeling with neuronal progenitor markers in vivo and in vitro show that EYFP-expressing cells are postmitotic and T alpha-1 tubulin EYFP precedes the expression of MAP-2 and NeuN, and follows the expression of PSA-NCAM, doublecortin (Dcx), and beta III-tubulin. T alpha-1 tubulin promoter-driven EYFP expression is transient and disappears in most neurons by PO. Persistent EYFP expression is mainly limited to scattered cells in the subventricular zone (SVZ), rostral migratory stream, and hippocampus. However, there are some areas that continue to express T alpha-1 tubulin in the adult without apparent neurogenesis. The number of EYFP-expressing cells declines with age indicating that T alpha-1 tubulin accurately identifies early born postmitotic neurons throughout development but less clearly in the adult. Assessment of neurogenesis after stab wound injuries in the cortex, cerebellum and spinal cord of adult animals shows no neurogenesis in most areas with an increase in BrdU incorporation in glial and other non neuronal populations. An up-regulation of T alpha-1 tubulin can be seen in certain areas unaccompanied by new neurogenesis. Our results suggest that even if stein cells proliferate their ability to generate neurons is limited and caution is warranted in attributing increased BrdU incorporation to stein cells or cells fated to be neurons even in neurogenic areas. (c) 2005 Elsevier Inc. All rights reserved.