Thyroid hormone effects on Krox-24 transcription in the post-natal mouse brain are developmentally regulated but are not correlated with mitosis

Krox-24 (NGFI-A, Egr-1) is an immediate-early gene encoding a zinc finger transcription factor. As Krox-24 is expressed in brain areas showing post-natal neurogenesis during a thyroid hormone (T-3)-sensitive period, we followed T-3 effects on Krox-24 expression in newborn mice. We analysed whether regulation was associated,vith changes in mitotic activity in the subventricular zone and the cerebellum, In vivo T-3-dependent Krox-24 transcription was studied by polyethylenimine-based gene transfer. T-3 increased transcription from the Krox-24 promoter in both areas studied at post-natal day 2, but was without effect at day 6, An intact thyroid hormone response element (TRE) in the Krox-24 promoter was necessary for these inductions. These stage-dependent effects were also seen in endogenous Krox-24 mRNA levels: activation at day 2 and no effect at day 6, Moreover, similar results were obtained by examining beta-galactosidase expression in heterozygous mice in which one allele of the Krox-24 gene was disrupted with an in-frame Lac-Z insertion. However, bromodeoxyuridine incorporation showed mitosis to continue through to day 6. We conclude first, that T-3 activates Krox-24 transcription during early post-natal mitosis but that this effect is extinguished as development proceeds and second, loss of T-3-dependent Krox-24 expression is not correlated with loss of mitotic activity.