@article{beattie_postiglione_burnett_laukoter_streicher_pauler_xiao_klezovitch_vasioukhin_ghashghaei_et al._2017, title={Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells}, volume={94}, DOI={10.1016/j.neuron.2017.04.012}, abstractNote={The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.}, number={3}, journal={Neuron (Cambridge, Mass.)}, author={Beattie, R. and Postiglione, M. P. and Burnett, L. E. and Laukoter, S. and Streicher, C. and Pauler, F. M. and Xiao, G. X. and Klezovitch, O. and Vasioukhin, V. and Ghashghaei, T. H. and et al.}, year={2017}, pages={517-} } @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} }