Co-ordination of cell cycle and differentiation in the developing nervous system

Abstract

During embryonic development, cells must divide to produce appropriate numbers, but later must exit the cell cycle to allow differentiation. How these processes of proliferation and differentiation are co-ordinated during embryonic development has been poorly understood until recently. However, a number of studies have now given an insight into how the cell cycle machinery, including cyclins, CDKs (cyclin-dependent kinases), CDK inhibitors and other cell cycle regulators directly influence mechanisms that control cell fate and differentiation. Conversely, examples are emerging of transcriptional regulators that are better known for their role in driving the differentiated phenotype, which also play complementary roles in controlling cell cycle progression. The present review will summarise our current understanding of the mechanisms co-ordinating the cell cycle and differentiation in the developing nervous system, where these links have been, perhaps, most extensively studied.

Figure 1. The cell cycle

The points at which specific cyclin–CDK complexes are active and where inhibitors or positive regulators of the cell cycle act are illustrated. cyc, cyclin.

Figure 2. G₁/S-phase transition

The role of negative regulators (CDKis and Rb) with respect to both cell cycle progression and development are highlighted. Cyc, cyclin; P, phosphorylation.

Figure 3. TGF-β signalling as a cytostatic signal

A focus on the role of Fox transcription factors in the decision to proliferate. Note how the expression of Fox factors links inhibition of proliferation with extracellular signalling and neural specification. An animation of this Figure is available at http://www.BiochemJ.org/bj/444/0375/bj4440375add.htm.