Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice.

Ajioka I, Martins RA, Bayazitov IT, Donovan S, Johnson DA, Frase S, Cicero SA, Boyd K, Zakharenko SS, Dyer MA
Cell. 2007 131 (2): 378-90

PMID: 17956737 · PMCID: PMC2203617 · DOI:10.1016/j.cell.2007.09.036

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.

MeSH Terms (14)

Animals Bone Marrow Neoplasms Brain Neoplasms Cell Differentiation Cell Division Interneurons Lymphatic Metastasis Mice Retina Retinal Neoplasms Retinoblastoma Retinoblastoma-Like Protein p107 Retinoblastoma Protein Stem Cells

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