Dedifferentiation of neurons precedes tumor formation in Lola mutants

Tony D Southall; Catherine M Davidson; Claire Miller; Adrian Carr; Andrea H Brand

doi:10.1016/j.devcel.2014.01.030

Dedifferentiation of neurons precedes tumor formation in Lola mutants

Dev Cell. 2014 Mar 31;28(6):685-96. doi: 10.1016/j.devcel.2014.01.030. Epub 2014 Mar 13.

Authors

Tony D Southall¹, Catherine M Davidson¹, Claire Miller¹, Adrian Carr¹, Andrea H Brand²

Affiliations

¹ The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
² 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Brain Neoplasms / genetics
Brain Neoplasms / pathology*
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Differentiation*
Drosophila Proteins / genetics
Drosophila Proteins / metabolism
Drosophila Proteins / physiology*
Drosophila melanogaster / genetics
Drosophila melanogaster / growth & development
Gene Expression Regulation, Developmental
Immunoenzyme Techniques
In Situ Hybridization
Mitosis / physiology
Neoplastic Stem Cells / pathology*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Neural Stem Cells / metabolism
Neural Stem Cells / pathology*
Neurons / cytology*
Neurons / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism
Transcription Factors / physiology*
Two-Hybrid System Techniques

Substances

Cell Cycle Proteins
Drosophila Proteins
Nerve Tissue Proteins
Nuclear Proteins
Transcription Factors
lola protein, Drosophila
pros protein, Drosophila

Abstract

Publication types

MeSH terms

Substances

Grants and funding