The retinoblastoma gene family in tumor suppression and development

The retinoblastoma tumor suppressor and the closely related p107 and p130 proteins play important roles in the regulation of both tumorigenesis and tissue-specific differentiation. To determine the role of Rb in development more precisely, we analyzed chimeric embryos and adults made with marked Rb-/- cells. We demonstrated that although brains of chimeric embryos exhibited extensive ectopic S-phase entry, unlike in germline Rb-/- littermates, in these chimeras the majority of Rb-deficient cells survived and differentiated into neuronal fates. Therefore, the role of Rb during development can be divided into a cell-autonomous function in exit from the cell cycle and a non-cell autonomous role in the suppression of apoptosis and induction of differentiation. Rb-/- ES cells were also able to efficiently differentiate into neurons in vitro. However, similarly to the situation observed in the chimeric embryos, Rb-/- neuronal cells failed to properly exit the cell cycle and continued to progress through the S-phase, while displaying fully differentiated neuronal morphology and expressing mature neuronal markers. Therefore, Rb function is not required for the commitment to the neuronal lineage or progression of neuronal differentiation but necessary for the cell cycle exit of differentiating neurons. In agreement, in wild-type differentiating ES cells, activity of the retinoblastoma protein (pRB) was increased specifically at the time of neuronal precursor cell cycle exit.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2002

Author dc:creator

• Lipinski, Marta M. (Marta Monika), 1971-

Advisor dc:contributor.advisor

• Tyler Jacks.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8317

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8317