Rb and p107 are required for normal cerebellar development and granule cell survival but not for Purkinje cell persistence.
The involvement of the retinoblastoma gene product (Rb) and its family members (p107 and p130) in cell cycle exit and terminal differentiation of neural precursor cells has been demonstrated in vitro. To investigate the roles of Rb and p107 in growth, differentiation and apoptosis in the developing and mature cerebellum, we selectively inactivated either Rb alone or in combination with p107 in cerebellar precursor cells or in Purkinje cells. In our mouse models, we show that (1) Rb is required for differentiation, cell cycle exit and survival of granule cell precursors; (2) p107 can not fully compensate for the loss of Rb function in granule cells; (3) Rb and p107 are not required for differentiation and survival of Purkinje cells during embryonic and early postnatal development; (4) Rb function in Purkinje cells is cell autonomous; and (5) loss of Rb deficient CNS precursor cells is mediated by p53-independent apoptosis.
Marino
Silvia
S
Institute of Clinical Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zürich, Switzerland. silvia.marino@usz.ch
Hoogervoorst
Dennis
D
Brandner
Sebastian
S
Berns
Anton
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107
D009687:Nuclear Proteins; C489485:Rbl1 protein, mouse; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107