title: Dedifferentiation of neurons precedes tumor formation in Lola mutants.
abstract: The ability to reprogram differentiated cells into a pluripotent state has revealed that the differentiated state is plastic and reversible. It is evident, therefore, that mechanisms must be in place to maintain cells in a differentiated state. Transcription factors that specify neuronal characteristics have been well studied, but less is known about the mechanisms that prevent neurons from dedifferentiating to a multipotent, stem cell-like state. Here, we identify Lola as a transcription factor that is required to maintain neurons in a differentiated state. We show that Lola represses neural stem cell genes and cell-cycle genes in postmitotic neurons. In lola mutants, neurons dedifferentiate, turn on neural stem cell genes, and begin to divide, forming tumors. Thus, neurons rather than stem cells or intermediate progenitors are the tumor-initiating cells in lola mutants.
authors.affiliation: The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Tony D
authors.initials: TD
authors.lastname: Southall
authors.affiliation: The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Davidson
authors.affiliation: The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Miller
authors.affiliation: The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Carr
authors.affiliation: The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Electronic address: a.brand@gurdon.cam.ac.uk.
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Brand
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008938:Mitosis / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C121765:lola protein, Drosophila; C073099:pros protein, Drosophila