Brain; Subventricular zone; Neurogenesis; Hippocampus; Neural stem cells
Boda Enrica, Di Maria Silvia, Rosa Patrizia, Taylor Verdon, Abbracchio Maria P., Buffo Annalisa (2015), Early Phenotypic Asymmetry of Sister Oligodendrocyte Progenitor Cells After Mitosis and Its Modulation by Aging and Extrinsic Factors, in GLIA
, 63(2), 271-286.
Moretti Francesca, Rolando Chiara, Winker Moritz, Ivanek Robert, Rodriguez Javier, Von Kriegsheim Alex, Taylor Verdon, Bustin Michael, Pertz Olivier (2015), Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth, in MOLECULAR AND CELLULAR BIOLOGY
, 35(11), 2035-2050.
Lojewski Xenia, Srimasorn Sumitra, Rauh Juliane, Francke Silvan, Wobus Manja, Taylor Verdon, Arauzo-Bravo Marcos J., Hallmeyer-Elgner Susanne, Kirsch Matthias, Schwarz Sigrid, Schwarz Johannes, Storch Alexander, Hermann Andreas (2015), Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential, in STEM CELLS TRANSLATIONAL MEDICINE
, 4(10), 1223-1233.
Nato Giulia, Caramello Alessia, Trova Sara, Avataneo Valeria, Rolando Chiara, Taylor Verdon, Buffo Annalisa, Peretto Paolo, Luzzati Federico (2015), Striatal astrocytes produce neuroblasts in an excitotoxic model of Huntington's disease, in DEVELOPMENT
, 142(5), 840-845.
Azim Kasum, Hurtado-Chong Anahi, Fischer Bruno, Kumar Nitin, Zweifel Stefan, Taylor Verdon, Raineteau Olivier (2015), Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone, in STEM CELLS
, 33(7), 2232-2242.
Rago Luciano, Beattie Robert, Taylor Verdon, Winter Jennifer (2014), miR379-410 cluster miRNAs regulate neurogenesis and neuronal migration by fine-tuning N-cadherin, in EMBO JOURNAL
, 33(8), 906-920.
Giachino Claudio, Basak Onur, Lugert Sebastian, Knuckles Philip, Obernier Kirsten, Fiorelli Roberto, Frank Stephan, Raineteau Olivier, Alvarez-Buylla Arturo, Taylor Verdon (2014), Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population, in STEM CELLS
, 32(1), 70-84.
Rolando Chiara, Taylor Verdon (2014), Neural Stem Cell of the Hippocampus: Development, Physiology Regulation, and Dysfunction in Disease, in STEM CELLS IN DEVELOPMENT AND DISEASE
, 107, 183-206.
Giachino Claudio, Taylor Verdon (2014), Notching up neural stem cell homogeneity in homeostasis and disease, in FRONTIERS IN NEUROSCIENCE
, 8, 32.
Wang Yidong, Wu Bingruo, Chamberlain Alyssa A., Lui Wendy, Koirala Pratistha, Susztak Katalin, Klein Diana, Taylor Verdon, Zhou Bin (2013), Endocardial to Myocardial Notch-Wnt-Bmp Axis Regulates Early Heart Valve Development, in PLOS ONE
, 8(4), e60244.
Giachino Claudio, Barz Michael, Tchorz Jan S., Tome Mercedes, Gassmann Martin, Bischofberger Josef, Bettler Bernhard, Taylor Verdon (2013), GABA suppresses neurogenesis in the adult hippocampus through GABA(B) receptors, in DEVELOPMENT
, 141(1), 83-90.
The regulation of neural stem cell (NSC) maintenance and differentiation is crucial for formation of the central nervous system (CNS). A detailed understanding of NSC biology has important implications for comprehending congenital brain malformations, age-related disorders, neurological diseases and regeneration. Established genetic tools, in vivo and in vitro experimental approaches for manipulation and lineage tracing, make neural progenitors an attractive experimental paradigm. The patterned and structured formation of the mammalian brain and positional fate restriction assists in the analysis of phenotypes and gene functions. Further, congenital brain malformations can often be traced to aberrant proliferation, differentiation or specification of neural progenitors. The production of new neurons also plays important roles in the adult mammalian brain. In rodents, neurons of the olfactory system are continually regenerated from the subventricular zone (SVZ), rebuilding complex multi-neuron circuits. New neurons in the hippocampal dentate gyrus (DG) are important for specific forms of memory and learning in mice. Although the role of neurogenesis in the human brain is debated, links to pathologies including epilepsy, depression and brain tumors underline the importance of understanding the mechanism controlling NSCs. The potential of NSC for regeneration and rejuvenation also emphasize a need to fill the gaps in our basic knowledge of NSC biology.My lab has focused on the role of Notch signaling in NSC maintenance1-4. By generating and combining transgenic mice with analysis of homeostasis, physical activity, degeneration, regeneration aging and in vitro approaches, we determined that NSCs are a heterogeneous cell population even within the same niche1,2,4-6. Recently, we found that the adult SVZ and DG contain active and dormant NSCs1,5-7. Active NSCs express brain lipid binding protein (BLBP), drive neurogenesis, and there loss is one potential cause of the age-dependent decline in neurogenesis. BLBP+ active NSCs have not been studied in detail, either during homeostasis, aging nor regeneration. We have generated tools including transgenic mice to study these active and dormant NSCs in greater detail. We will use these tools to continue to deepen our knowledge of NSCs in the brain. We will lineage trace different NSC populations in vivo, addressing dormant, quiescent and active NSCs and elucidating their roles in homeostasis and regeneration. We will study the effects that pathophysiological stimuli have on these NSC populations. Recently we found that active NSCs depend upon Notch1 but dormant NSCs do not. Dormant NSCs express Notch2 and Notch3, hence, we will assess the functions of Notch1, Notch2 and Notch3 in the different NSCs populations of the brain. The control of NSC activity and dormancy has clinical relevance for regeneration but also for rejuvenation to combat age-related disorders. We have generated transcription profiles of embryonic and adult Hes5::GFP+ NSCs and of Notch1-regulated genes in NSCs. Many components of the microRNA (miRNA) biogenesis pathway were present in these profiles. Therefore, we targeted the root of miRNA biogenesis, conditionally ablating key components of the miRNA microprocessor (MP) in forebrain NSCs. We established that the MP and Drosha, unlike Dicer, play a central role in regulating NSCs during development. An important function of the MP in NSCs is a novel miRNA-independent mechanism to directly target stem-loop hairpin structures in the Ngn2 mRNA. We will extend our previous findings of MP function in neurogenesis, identify novel targets of the MP and extend the analysis of MP function to active and dormant NSCs during aging and regeneration.