Inducible deletion of Smad4 in adult astrocytes and neural stem cells in the adult SEZ. A, B, In situ hybridization of Smad4 mRNA in the adult SEZ 10 d after activation of CreERT2 expressed in the GLAST locus (GLAST:CreERT2) by tamoxifen in mice without (A) or with (B) exon 8 of Smad4 flanked by loxP sites. Note the loss of Smad4 mRNA in B versus A. C, D, Fluorescent micrographs of p-Smad1/5/8 immunostaining in GLAST:CreERT2 mice WT for the Smad4 locus (C) or homozygous for the floxed exon 8 of Smad4 (D) 10 d after induction of Cre-mediated recombination by tamoxifen. Note the widespread loss of nuclear localization of p-Smad1/5/8 after deletion of Smad4 (D). The arrows in D indicate some of the remaining p-Smad1/5/8+ cells also demonstrating the same quality of immunostaining. LV, Lateral ventricle; D, dorsal; V, ventral; R, rostral; C, caudal. Scale bars: (in B) A, B, 100 μm; (in D) C, D, 100 μm.