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Updated: Jul 14, 2026
Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis
Published on: December 18, 2019
Cooperation between p27 and p107 during endochondral ossification suggests a genetic pathway controlled by p27 and
Nancy Yeh1, Jeffrey P Miller, Tripti Gaur
1Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Abstract:
Pocket proteins and cyclin-dependent kinase (CDK) inhibitors negatively regulate cell proliferation and can promote differentiation. However, which members of these gene families, which cell type they interact in, and what they do to promote differentiation in that cell type during mouse development are largely unknown. To identify the cell types in which p107 and p27 interact, we generated compound mutant mice. These mice were null for p107 and had a deletion in p27 that prevented its binding to cyclin-CDK complexes. Although a fraction of these animals survived into adulthood and looked similar to single p27 mutant mice, a larger number of animals died at birth or within a few weeks thereafter. These animals displayed defects in chondrocyte maturation and endochondral bone formation. Proliferation of chondrocytes was increased, and ectopic ossification was observed. Uncommitted mouse embryo fibroblasts could be induced into the chondrocytic lineage ex vivo, but these cells failed to mature normally. These results demonstrate that p27 carries out overlapping functions with p107 in controlling cell cycle exit during chondrocyte maturation. The phenotypic similarities between p107(-/-) p27(D51/D51) and p107(-/-) p130(-/-) mice and the cells derived from them suggest that p27 and p130 act in an analogous pathway during chondrocyte maturation.
Insights
p27 and p107 proteins regulate cell cycle exit in developing mouse chondrocytes. Loss of p27 function overlaps with p107, impacting chondrocyte maturation and bone formation.
Area of Science:
- Cell biology
- Developmental biology
- Molecular biology
Background:
- Pocket proteins and cyclin-dependent kinase (CDK) inhibitors regulate cell proliferation and differentiation.
- The specific roles of these proteins in mouse development, particularly in cell-type-specific differentiation, remain largely unknown.
Purpose of the Study:
- To identify cell types where p107 and p27 interact.
- To elucidate the functions of p107 and p27 in chondrocyte maturation and endochondral bone formation during mouse development.
Main Methods:
- Generation of compound mutant mice lacking functional p107 and a p27 variant unable to bind cyclin-CDK complexes.
- Phenotypic analysis of mutant mice, including assessment of survival, chondrocyte maturation, and bone formation.
- In vitro induction of chondrogenesis from mouse embryo fibroblasts.
Main Results:
- Compound mutant mice exhibited embryonic lethality or early postnatal death with defects in chondrocyte maturation and endochondral ossification.
- Increased chondrocyte proliferation and ectopic ossification were observed in mutant mice.
- Induced chondrocytes from mutant fibroblasts failed to mature properly, indicating a cell-autonomous role for p27 and p107.
Conclusions:
- p27 plays overlapping roles with p107 in controlling cell cycle exit during chondrocyte maturation.
- p27 and p130 appear to function in an analogous pathway critical for chondrocyte differentiation and skeletal development.
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