Differentiated Horizontal Interneurons Clonally Expand to Form Metastatic Retinoblastoma in Mice

During neurogenesis, the progression from a progenitor cell to a differentiated neuron is believed to be unidirectional and irreversible. The Rb family of proteins (Rb, p107, and p130) regulates cell-cycle exit and differentiation during retinogenesis. Rb and p130 are redundantly expressed in the ne...

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Bibliographic Details
Published in:Cell 2007-10, Vol.131 (2), p.378-390
Main Authors: Ajioka, Itsuki, Martins, Rodrigo A.P., Bayazitov, Ildar T., Donovan, Stacy, Johnson, Dianna A., Frase, Sharon, Cicero, Samantha A., Boyd, Kelli, Zakharenko, Stanislav S., Dyer, Michael A.
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Neoplasms - pathology
Bone Marrow Neoplasms - secondary
Brain Neoplasms - pathology
Brain Neoplasms - secondary
Cell Differentiation
Cell Division
CELLBIO
CELLCYCLE
HUMDISEASE
Interneurons - metabolism
Interneurons - physiology
Lymphatic Metastasis
Mice
Retina - pathology
Retinal Neoplasms - pathology
Retinoblastoma - pathology
Retinoblastoma - secondary
Retinoblastoma Protein - genetics
Retinoblastoma Protein - physiology
Retinoblastoma-Like Protein p107 - genetics
Retinoblastoma-Like Protein p107 - physiology
Stem Cells - metabolism
Stem Cells - physiology
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Summary:During neurogenesis, the progression from a progenitor cell to a differentiated neuron is believed to be unidirectional and irreversible. The Rb family of proteins (Rb, p107, and p130) regulates cell-cycle exit and differentiation during retinogenesis. Rb and p130 are redundantly expressed in the neurons of the inner nuclear layer (INL) of the retina. We have found that in the adult Rb;p130-deficient retinae p107 compensation prevents ectopic proliferation of INL neurons. However, p107 is haploinsufficient in this process. Differentiated Rb −/−;p107 +/−;p130 −/− horizontal interneurons re-entered the cell cycle, clonally expanded, and formed metastatic retinoblastoma. Horizontal cells were not affected in Rb +/−;p107 −/−;p130 −/− or Rb −/−;p107 −/−;p130 +/− , retinae suggesting that one copy of Rb or p130 was sufficient to prevent horizontal proliferation. We hereby report that differentiated neurons can proliferate and form cancer while maintaining their differentiated state including neurites and synaptic connections.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2007.09.036