Cell cycle regulators in neural stem cells and postmitotic neurons.

Abstract

In the mammalian central nervous system, neurons withdraw from the cell cycle immediately after their differentiation from proliferative neuroepithelial cells. Even while postmitotic neurons remain in permanent mitotic quiescence, they express a number of cell cycle regulators required for cell cycle progression. This review focuses on the expression and functions of members of the retinoblastoma protein (Rb) family (Rb, p107, p130) and necdin, all of which are growth suppressors that interact with the viral oncoproteins and the E2F family proteins. These molecules are differentially expressed in proliferative neural progenitors and postmitotic neurons in the developing neuroepithelium in vivo and differentiating embryonal carcinoma cells in vitro. During neurogenesis, dysfunction of the Rb family proteins causes impaired neuronal differentiation accompanied by cell death (apoptosis). Thus, the Rb family proteins are essential for both terminal mitosis of neuronal progenitors and survival of nascent neurons. However, the Rb family proteins seem to be dispensable for the maintenance of the postmitotic state of terminally differentiated neurons. Necdin is expressed exclusively in postmitotic cells and may contribute to their permanent mitotic arrest. These cell cycle regulators coordinately act in the generation, survival and demise of postmitotic neurons.