Faculty Bibliography

OBJECTIVE: Our objective is to exploit architectural constraint for the analysis and interpretation of craniofacial form, which we apply here to the reconstruction of the early Homo cranium KNM-ER 1470. We are motivated to perform this study because in the absence of biological criteria our preconceptions are likely to govern our concept of craniofacial form. STUDY DESIGN: We reassembled the fragmented parts--left and right halves of the calvaria and the face--according to mammalian craniofacial architectural constraints described by Donald H. Enlow and colleagues. RESULTS: When evaluated on a biological premise, KNM-ER 1470 is found to have a more prognathic midface than commonly appreciated. The relationship between facial prognathism and cranial capacity also provides an estimate downward for this specimen, from 752cc to ca. 700cc. CONCLUSION: Awareness of our preconceptions is critical to the performance of relatively unbiased research in fields characterized by interpretations of morphology. When perceptual bias is relatively minimized, applied here as an architecturally constrained of KNM-ER 1470 craniofacial skeleton, we are able to provide the scientific community with a more tractable Gestalt perspective of form

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