The Role of CDKs and CDKIs in Murine Development

Abstract

Cyclin-dependent kinases (CDKs) and their inhibitors (CDKIs) play pivotal roles in the regulation of the cell cycle. As a result of these functions, it may be extrapolated that they are essential for appropriate embryonic development. The twenty known mouse CDKs and eight CDKIs have been studied to varying degrees in the developing mouse, but only a handful of CDKs and a single CDKI have been shown to be absolutely required for murine embryonic development. What has become apparent, as more studies have shone light on these family members, is that in addition to their primary functional role in regulating the cell cycle, many of these genes are also controlling specific cell fates by directing differentiation in various tissues. Here we review the extensive mouse models that have been generated to study the functions of CDKs and CDKIs, and discuss their varying roles in murine embryonic development, with a particular focus on the brain, pancreas and fertility.

Keywords: CDK inhibitors; cyclin-dependent kinase; development; knock-out models; mouse.

Figure 1

Schematic of principal areas of CDK and CDKI involvement during murine development, as determined by KO and cKO mouse models. The ears, brain, pituitary gland, eyes, spine, lungs, heart, liver, pancreas, kidneys, spleen, intestine and testes/ovaries are colour-coded based on the presence of an altered phenotype upon KO of a CDK or CDKI, depicted here in an E17.5 mouse embryo. The area of each colour is not reflective of the magnitude of the effect on the mouse phenotype. KOs of Cdk1, Cdk4, Cdk6, Cdk11, Cdk13, Cdkn1b, Cdkn1c and Cdkn2c affect overall embryonic development.