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Cyclin-dependent kinase 5 is associated with apoptotic cell death during development and tissue remodeling
Q Zhang1, H S Ahuja, Z F Zakeri
1Department of Genetics, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Abstract:
In a series of studies to more precisely localize the cellular sites of expression of the cyclin-dependent kinase (Cdk) family members in reproductive organs, we observed a striking expression of Cdk5 in atretic follicles in the ovary, particularly in granulosa cells that appeared to be dying. We determined that these granulosa cells were undergoing apoptotic cell death using the in situ DNA fragmentation assay. To extend the generality of the association of Cdk5 with apoptotic cells, we examined its expression as it correlated with the detection of apoptosis in a number of developmental paradigms, including regions of the embryonic nervous system, the developing eye, and the developing limb. Finally, the association of apoptosis and Cdk5 expression and associated kinase activity was examined in the limb and in an induced cell death system, that of androgen withdrawal-induced regression of the prostate gland in male mice. These observations provide new insight into the possible function of this novel Cdk during both differentiation and apoptotic cell death.
Insights
Cyclin-dependent kinase 5 (Cdk5) is expressed in dying ovarian cells and other apoptotic cells during development. This suggests Cdk5 plays a role in cell death and differentiation.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Cyclin-dependent kinases (Cdks) are crucial regulators of the cell cycle.
- The specific roles of Cdk5 in reproductive organs and cell death pathways are not fully understood.
Purpose of the Study:
- To investigate the cellular localization of Cdk5 expression in reproductive organs.
- To determine the association of Cdk5 with apoptotic cell death in various developmental contexts.
Main Methods:
- In situ DNA fragmentation assay to detect apoptosis.
- Immunohistochemical analysis of Cdk5 expression in ovarian follicles, embryonic tissues, and prostate glands.
Main Results:
- Cdk5 was highly expressed in granulosa cells of atretic ovarian follicles undergoing apoptosis.
- Cdk5 expression correlated with apoptosis in the embryonic nervous system, eye, and limb development.
- Cdk5 expression and kinase activity were observed in the prostate gland during androgen withdrawal-induced regression.
Conclusions:
- Cdk5 is specifically expressed in apoptotic cells within the ovary and during embryonic development.
- These findings suggest a novel role for Cdk5 in regulating both cell differentiation and apoptotic cell death.