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Oral Biosciences & Medicine

Edited by Birgitte Nauntofte, Jesper Reibel. Peter A. Reichart, Jim Sciubba, and Joanna M. Zakrzewska

Official publication of the European Society for Oral Laser Applications

ISSN 1742-3287

Oral Biosciences & Medicine

Year 2005
Volume 2 , Issue 2

Pages: 57 - 65

Genetic and Epigenetic Determinants of Skeletal Morphogenesis - Role of Cellular Polarity and Ciliary Function in Skeletal Development and Growth

Olsen, Bjorn R./Kolpakova, Elona/McBratney-Owen, Brandeis/Li, Xiaogang/Zhou, Jing/Fukai, Naomi

This review discusses evidence that proteins involved in establishing and maintaining polarity and/or primary cilia in cells have essential roles in skeletal morphogenesis and growth. It is argued that fibroblasts, chondrocytes and osteoblasts have a secretory polarity defined by the location of the trans-Golgi network and that the primary cilium is a good marker for the secretory apical region of the cells. It has been demonstrated that primary cilia in epithelial cells function as mechanosensors in that they can activate a Ca++ -permeant channel complex composed of the transmembrane proteins polycystin-1 and polycystin-2 when exposed to fluid flow or physical bending forces. It has therefore been proposed that primary cilia may also have mechanosensing functions in skeletal cells. To test this hypothesis, we have conditionally inactivated the genes encoding Kif3a, a motor protein required for cell polarity and assembly of the primary cilium, and polycystin-1. Mice carrying floxed alleles of these genes have been crossed with mice that express cre recombinase under the control of promoters that are active at an early stage in cranial neural crest cells, in early limb bud mesenchyme, or in cells of mesodermal origin of both limbs and skull.
Conclusions: The mutant phenotypes are consistent with the conclusion that protein complexes involved in cell polarity and assembly of primary cilia, including the motor protein Kif3a, are essential for hedgehog-mediated craniofacial and appendicular morphogenetic processes, and that polycystin-1 is required for normal development and postnatal function of sutures and specific synchondroses of the vertebrate skull.

Keywords: primary cilia, cellular polarity, skeletal morphogenesis, hedgehog signalling, polydactyly, growth plate, synchondrosis


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