@article{liang_xiao_yin_hippenmeyer_horowitz_ghashghaei_2013, title={Neural development is dependent on the function of specificity protein 2 in cell cycle progression}, volume={140}, ISSN={["0950-1991"]}, DOI={10.1242/dev.085621}, abstractNote={Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.}, number={3}, journal={DEVELOPMENT}, author={Liang, Huixuan and Xiao, Guanxi and Yin, Haifeng and Hippenmeyer, Simon and Horowitz, Jonathan M. and Ghashghaei, H. Troy}, year={2013}, month={Feb}, pages={552–561} } @article{jacquet_muthusamy_sommerville_xiao_liang_zhang_holtzman_ghashghaei_2011, title={Specification of a Foxj1-Dependent Lineage in the Forebrain Is Required for Embryonic-to-Postnatal Transition of Neurogenesis in the Olfactory Bulb}, volume={31}, ISSN={["0270-6474"]}, DOI={10.1523/jneurosci.0171-11.2011}, abstractNote={Establishment of a neural stem cell niche in the postnatal subependymal zone (SEZ) and the rostral migratory stream (RMS) is required for postnatal and adult neurogenesis in the olfactory bulbs (OB). We report the discovery of a cellular lineage in the SEZ-RMS-OB continuum, the specification of which is dependent on the expression of the forkhead transcription factor Foxj1 in mice. Spatially and temporally restricted Foxj1+ neuronal progenitors emerge during embryonic periods, surge during perinatal development, and are active only for the first few postnatal weeks. We show that the development of the unique Foxj1-derived lineage is dependent on Foxj1 expression and is required for overall postnatal neurogenesis in the OB. Strikingly, the production of neurons from Foxj1+ progenitors significantly declines after the early postnatal weeks, but Foxj1-derived neurons in the OB persist during adult periods. For the first time, our study identifies the time- and region-specific activity of a perinatal progenitor domain that is required for transition and progression of OB neurogenesis from the embryonic-to-postnatal periods.}, number={25}, journal={JOURNAL OF NEUROSCIENCE}, author={Jacquet, Benoit V. and Muthusamy, Nagendran and Sommerville, Laura J. and Xiao, Guanxi and Liang, Huixuan and Zhang, Yong and Holtzman, Michael J. and Ghashghaei, H. Troy}, year={2011}, month={Jun}, pages={9368–9382} } @article{jacquet_patel_iyengar_liang_therit_salinas-mondragon_lai_olsen_anton_ghashghaei_2009, title={Analysis of neuronal proliferation, migration and differentiation in the postnatal brain using equine infectious anemia virus-based lentiviral vectors}, volume={16}, ISSN={["1476-5462"]}, DOI={10.1038/gt.2009.58}, abstractNote={Ongoing neurogenesis in discrete sectors of the adult central nervous system depends on the mitotic activity of an elusive population of adult stem cells. The existence of adult neural stem cells provides an alternative approach to transplantation of embryonic stem cells in cell-based therapies. Owing to the limited intrinsic fate of adult stem cells and inhibitory nature of the adult brain for neurogenesis, accommodation for circuit replacement in the brain will require genetic and epigenetic manipulation. Here, we show that a replication-incompetent Equine Infectious Anemia Virus (EIAV) is highly suitable for stable and persistent gene transfer to adult neural stem cells. The transduced regions were free of long-lasting neuroimmune responses to EIAV. Transduction in the subventricular zone was specific to the stem cell niche, but spared the progeny of adult neural stem cells that includes transit amplifying progenitors (TAPs) and migrating neuroblasts. With time, EIAV-transduced stem cells passed on the transgene to TAPs and migrating neuroblasts, which ultimately differentiated into neurons in the olfactory bulbs. We show that EIAV is highly suitable for discovery and assessment of mechanisms that regulate proliferation, migration and differentiation in the postnatal brain.}, number={8}, journal={GENE THERAPY}, author={Jacquet, B. V. and Patel, M. and Iyengar, M. and Liang, H. and Therit, B. and Salinas-Mondragon, R. and Lai, C. and Olsen, J. C. and Anton, E. S. and Ghashghaei, H. T.}, year={2009}, month={Aug}, pages={1021–1033} } @article{jacquet_salinas-mondragon_liang_therit_buie_dykstra_campbell_ostrowski_brody_ghashghaei_2009, title={FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain}, volume={136}, ISSN={["1477-9129"]}, DOI={10.1242/dev.041129}, abstractNote={Neuronal specification occurs at the periventricular surface of the embryonic central nervous system. During early postnatal periods, radial glial cells in various ventricular zones of the brain differentiate into ependymal cells and astrocytes. However, mechanisms that drive this time- and cell-specific differentiation remain largely unknown. Here, we show that expression of the forkhead transcription factor FoxJ1 in mice is required for differentiation into ependymal cells and a small subset of FoxJ1+ astrocytes in the lateral ventricles, where these cells form a postnatal neural stem cell niche. Moreover, we show that a subset of FoxJ1+ cells harvested from the stem cell niche can self-renew and possess neurogenic potential. Using a transcriptome comparison of FoxJ1-null and wild-type microdissected tissue, we identified candidate genes regulated by FoxJ1 during early postnatal development. The list includes a significant number of microtubule-associated proteins, some of which form a protein complex that could regulate the transport of basal bodies to the ventricular surface of differentiating ependymal cells during FoxJ1-dependent ciliogenesis. Our results suggest that time- and cell-specific expression of FoxJ1 in the brain acts on an array of target genes to regulate the differentiation of ependymal cells and a small subset of astrocytes in the adult stem cell niche.}, number={23}, journal={DEVELOPMENT}, author={Jacquet, Benoit V. and Salinas-Mondragon, Raul and Liang, Huixuan and Therit, Blair and Buie, Justin D. and Dykstra, Michael and Campbell, Kenneth and Ostrowski, Lawrence E. and Brody, Steven L. and Ghashghaei, H. Troy}, year={2009}, month={Dec}, pages={4021–4031} }