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.
Highlights
Cyclin-dependent kinases (CDKs) are proteins that, by definition, require the binding of partner cyclin proteins in order to phosphorylate a series of target proteins
This review aims to summarise the known functions of CDKs and CDK inhibitors (CDKIs) in murine development, with a particular focus on development of the brain, pancreas, sperm and oocytes, principally using information gained from mouse models
Alternative splicing of Cdkn2c leads to two distinct mRNAs, the shorter of which is found in various differentiated cell types such as muscle, lung and liver, while the longer mRNA is isolated to the testes in undifferentiated, mitotically active cells, suggesting that the two protein isotypes have separate roles, for differentiation [126]. p15INK4a, p16INK4b, p21CIP1 and p27KIP1 are all expressed in the ovary, but p16INK4b is expressed more highly than the other CDKIs and seems to decrease during oocyte growth [127]
Summary
Cyclin-dependent kinases (CDKs) are proteins that, by definition, require the binding of partner cyclin proteins in order to phosphorylate a series of target proteins. Many CDKIs have been shown to play key roles in embryonic development [11,12,13] In addition to their shared ability to modulate the cell cycle, several of these CDKs and CDKIs have been shown to direct differentiation of a number of different cell types with a particular convergence in the brain, pancreas and gonadal ridges, which will be discussed in greater detail later on. For many of these proteins, their functions have been studied primarily through knock-out (KO) mouse models and cell lines. Embryo lethal due to heart defect [45]
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