title: The Snail transcription factor regulates the numbers of neural precursor cells and newborn neurons throughout mammalian life.
abstract: The Snail transcription factor regulates diverse aspects of stem cell biology in organisms ranging from Drosophila to mammals. Here we have asked whether it regulates the biology of neural precursor cells (NPCs) in the forebrain of postnatal and adult mice, taking advantage of a mouse containing a floxed Snail allele (Snailfl/fl mice). We show that when Snail is inducibly ablated in the embryonic cortex, this has long-term consequences for cortical organization. In particular, when Snailfl/fl mice are crossed to Nestin-cre mice that express Cre recombinase in embryonic neural precursors, this causes inducible ablation of Snail expression throughout the postnatal cortex. This loss of Snail causes a decrease in proliferation of neonatal cortical neural precursors and mislocalization and misspecification of cortical neurons. Moreover, these precursor phenotypes persist into adulthood. Adult neural precursor cell proliferation is decreased in the forebrain subventricular zone and in the hippocampal dentate gyrus, and this is coincident with a decrease in the number of adult-born olfactory and hippocampal neurons. Thus, Snail is a key regulator of the numbers of neural precursors and newborn neurons throughout life.
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada; Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zander
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Gonzalo I
authors.initials: GI
authors.lastname: Cancino
authors.affiliation: Maine Medical Center Research Institute, University of Maine, Scarborough, Maine, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gridley
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada; Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Kaplan
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada; Institute for Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Freda D
authors.initials: FD
authors.lastname: Miller
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D003433:Crosses, Genetic; D018891:Dentate Gyrus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D016548:Prosencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C577485:Nes protein, mouse; D064231:Nestin; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C000604451:sna protein, Drosophila; C045073:Cre recombinase; D019426:Integrases