Endotoxin-free plasmid DNA was diluted in 5% glucose and complexed with in vivo-jetPEI, ratio of 6 PEI nitrogen per DNA phosphate. Stereotaxic injection into the lateral ventricles of newborn mice brains was as described using a single injection (1 µg DNA in 2 µl) per lateral ventricle of newborn mice. Mice were sacrificed and the SVZ was dissected 24 hr later. Luciferase assays were done on brain homogenates.

The subventricular zone (SVZ) neural stem cell niche contains mixed populations of stem cells, transit-amplifying cells, and migrating neuroblasts. Deciphering how endogenous signals, such as hormones, affect the balance between these cell types is essential for understanding the physiology of niche plasticity and homeostasis. We show that Thyroid Hormone (T(3)) and its receptor, TRalpha1, are directly involved in maintaining this balance. TRalpha1 is expressed in amplifying and migrating cells. In vivo gain- and loss-of-function experiments demonstrate first, that T(3)/TRalpha1 directly repress Sox2 expression, and second, that TRalpha1 overexpression in the niche favors the appearance of DCX+ migrating neuroblasts. Lack of TRalpha increases numbers of SOX2+ cells in the SVZ. Hypothyroidism increases proportions of cells in interphase. Thus, in the adult SVZ, T(3)/TRalpha1 together favor neural stem cell commitment and progression toward a migrating neuroblast phenotype; this transition correlates with T(3)/TRalpha1-dependent transcriptional repression of Sox2.