title: Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice.
abstract: 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.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
authors.forename: Itsuki
authors.initials: I
authors.lastname: Ajioka
authors.forename: Rodrigo A P
authors.initials: RA
authors.lastname: Martins
authors.forename: Ildar T
authors.initials: IT
authors.lastname: Bayazitov
authors.forename: Stacy
authors.initials: S
authors.lastname: Donovan
authors.forename: Dianna A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Sharon
authors.initials: S
authors.lastname: Frase
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Cicero
authors.forename: Kelli
authors.initials: K
authors.lastname: Boyd
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Zakharenko
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dyer
mesh_terms: D000818:Animals; D019046:Bone Marrow Neoplasms / Q000473:pathology / Q000556:secondary; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary; D002454:Cell Differentiation; D002455:Cell Division; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D008207:Lymphatic Metastasis; D051379:Mice; D012160:Retina / Q000473:pathology; D019572:Retinal Neoplasms / Q000473:pathology*; D012175:Retinoblastoma / Q000473:pathology / Q000556:secondary*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: C489485:Rbl1 protein, mouse; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107